Research progress on pathogenesis of skin graft-versus-host disease / 器官移植

Graft-versus-host disease (GVHD) is a major cause that prevents widespread application of allogeneic hematopoietic stem cell transplantation. GVHD is a complication that can affect all systems of the body, such as skin, liver, lung and gastrointestinal tract, among which skin is the most vulnerable organ. At present, the pathogenesis of skin GVHD has not been fully elucidated, and no effective treatment has been established. Severe or extensive chronic GVHD significantly affects the quality of life of the recipients. Consequently, it is urgent to unravel the pathogenesis of skin GVHD and explore novel therapeutic treatment. Cytokines, such as interleukin (IL)-22, IL-17, IL-6 and interferon (IFN)-γ, have been proven to play pivotal roles in the progression of skin GVHD. Nevertheless, the specific mechanism remains elusive. In this article, research progresses at home and abroad on the mechanism underlying the roles of these cytokines in skin GVHD were reviewed, aiming to provide novel ideas for the prevention and treatment of skin GVHD.

Effects of IL-22 on hepatic ischemia-reperfusion injury and related mechanism in SD rats / 中华肝胆外科杂志

Objective:To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury (IRI) and the potential mechanisms.Methods:Eighteen male specific pathogen free SD rats (7-8 weeks, about 250g) were randomly divided into three groups: Sham group (Sham), hepatic ischemia reperfusion (IRI) and IL-22 preconditioning group (IL-22+ IRI), respectively. The liver IRI model of 70% rats was established. The IL-22+ IRI group was intraperitoneally injected with rcIL-22 (50 mg/kg) 1 hour before surgery, and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery. After 1 h ischemia and 6 h reperfusion, blood was collected from the abdominal aorta, then liver tissue, serum aspartate transaminase (AST) and alanine aminotransfease (ALT) levels were measured. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The expression of signal transducer and activator of transcription 3 (STAT3), p-STAT3, nuclear factor erythorid-2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blot. Results:Compared with Sham group, serum AST [(1 923.50±92.63) U/L, (1 004.25±65.05) U/L)] and ALT [(1 172.51±180.31) U/L, (583.50±164.75) U/L] levels were increased in IRI group and IL-22+ IRI group (AST: F=293.62; ALT: F=30.33, P<0.05). The levels of MDA in IRI group and IL-22+ IRI group [(1.72±0.12) μmol/mg, (0.98±0.05) μmol/mg] in liver tissue were higher than those in Sham group (0.58±0.14) μmol/mg protein ( F=186.73, P<0.05), and the expression of p-STAT3, Nrf2 and HO-1 was increased. SOD level in IRI group (28.51±3.85) U/mg was lower than that in Sham group (70.25±5.64) U/mg protein ( F=203.41, P<0.05). Compared with IRI group, serum AST and ALT levels in IL-22+ IRI group were decreased, SOD activity in liver tissue was increased, MDA level was decreased, and p-STAT3, Nrf2 and HO-1 expression was increased (all P<0.05). Conclusion:IL-22 could alleviate liver IRI in rats, and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.

Therapeutic effect of Yupingfeng powder combined with extensively hydrolyzed milk formulas on milk protein allergy in infants / 中国基层医药

Objective:To investigate the efficacy of Yupingfeng powder combined with extensively hydrolyzed milk formulas in the treatment of milk protein allergy in infants and its effects on immune function, interleukin-10 (IL-10) and IL-22 levels. Methods:Eighty infants with milk protein allergy who received treatment in Hangzhou Children's Hospital from January 2020 to January 2021 were included in this study. They were randomly assigned to Yupingfeng powder and conventional treatment groups, with 40 infants per group. An additional 80 infants who concurrently received health examination in the same hospital were included in the control group. The conventional group was treated with extensively hydrolyzed milk formulas. The Yupingfeng powder group was treated with Yupingfeng powder combined with extensively hydrolyzed milk formulas. All infants were treated for 30 successive days. Clinical efficacy, serum total immunoglobulin (IgE), milk specific IgE (sIgE), peripheral blood CD 4+CD 25+ Treg, IL-10 and IL-22 levels were compared between groups. Results:Total response rate in the Yupingfeng powder group was significantly higher than that in the conventional treatment group [92.50% (37/40) vs. 72.50% (29/40), χ2 = 5.54, P < 0.05]. Serum total IgE and milk sIgE levels in the Yupingfeng powder group were (132.93 ± 14.61) IU/L and (0.62 ± 0.14) IU/L, respectively, which were significantly lower than (150.27 ± 16.22) IU/L and (0.85 ± 0.17) IU/L in the conventional treatment group ( t = 5.02, 6.61, both P < 0.05). The expression of CD 4+CD 25+ Treg in the Yupingfeng powder group was significantly higher than that in the conventional treatment group [(13.29 ± 1.40)% vs. (11.84 ± 1.27)%, t = 4.85, P < 0.05). CD 4+CD 25+ Treg expression in the Yupingfeng powder group was not significantly different from that in the control group [(13.40 ± 2.03)%, t = 0.31, P = 0.759]. IL-10 in the Yupingfeng powder group was significantly higher than that in the conventional treatment group [(34.57 ± 4.07) μg/L vs. (22.19 ± 2.15) μg/L, t = 17.01, P < 0.05]. IL-22 level in the Yupingfeng powder group was significantly lower than that in the conventional treatment group [(2.20 ± 0.42) ng/L vs. (5.28 ± 0.79) ng/L, t = 21.77, P < 0.05]. IL-10 and IL-22 levels in the Yupingfeng powder group were not different from those in the control group [(35.53 ± 3.85) μg/L, (2.13 ± 0.53) ng/L, t = 1.26, P = 0.209; t = 0.73, P = 0.468]. Conclusion:Yupingfeng powder combined with extensively hydrolyzed milk formulas is highly effective on milk protein allergy. The combined therapy can improve the immune function of infants, enhance IL-10 level, and decrease IL-22 level.

Expression and significance of IL-17, IL-23 and IL-22 in rats with Klebsiella pneumoniae pneumonia / 国际生物医学工程杂志

Objective:To analyze the expression and significance of interleukin-17 (IL-17), IL-23 and IL-22 in Klebsiella pneumoniae (KPN) pneumonia in rats. Methods:A total of 40 male SPF rats were randomly divided into the control group and the experimental group according to the simple number random table method, with 20 rats in each group. The control group was simultaneously dropped with 2 mL normal saline, while the experimental group was inoculated with a 2 mL suspension of 0.9×10 9 CFU/mL. The lung tissue was taken for pathological and bacteriological examination. Arterial partial pressure of oxygen (PaO 2), serum IL-17, IL-23 and IL-22 levels were detected after surgery for 4 h, 1 d, 3 d and 5 d. White blood cell count (WBC) and absolute neutrophil count (ANC) were performed in bronchoalveolar lavage fluid (BALF), and the relevance between IL-17, IL-23, IL-22 and PaO 2, and WBC, ANC in BALF was analyzed. Results:After surgery for 4 h, 1 d, 3 d and 5 d, the CFU count of lung tissue in experimental group rats decreased over time. PaO 2 in experimental group was significantly lower than that in the control group after surgery for 4 h, 1 d, 3 d and 5 d ( P<0.05), while WBC and ANC in BALF in the experimental group were significantly higher at the same time ( P<0.05). The levels of IL-17 and IL-23 in serum in the experimental groups were significantly higher than those in the control group after surgery for 4 h, 1 d, 3 d and 5 d ( P<0.05), and the levels of IL-22 in serum in the experimental groups were significantly lower than those in the control group at the same time ( P<0.05). Pearson analysis showed that IL-17 and IL-23 were negatively correlated with PaO 2 ( P<0.05) and positively correlated with WBC and ANC ( P<0.05). IL-22 was positively correlated with PaO 2 ( P<0.05), and negatively correlated with WBC and ANC ( P<0.05). Conclusions:Serum IL-17, IL-23, and IL-22 levels were significantly altered during the course of KPN rats, and serum IL-17, IL-23, and IL-22 levels were correlated with severity of illness.

Advances on roles of Th22 cells in human common viral infections / 中华临床感染病杂志

Na?ve CD4 + T cells differentiate into a variety of T helper (Th) subsets that secrete various cytokines to exert biological effects. Th22 cells, a novel identified CD4 + T cell subset, are distinct from Th1, Th2 and Th17 cell subsets. Th22 cells express chemokine receptors CCR4, CCR6 and CCR10, and secrete multiple cytokines such as IL-22, IL-13 and TNF-α, but not IL-17, IL-4 IFN-γ; and IL-22 is considered as major effector cytokine of Th22. The understanding on functions and differentiation mechanisms of Th22 cells have been constantly improved, and Th22 cells play important roles in human common viral infections. The article reviews the current advances about the characteristics, function, differentiation of Th22 cells, the roles of Th22 cells and the key molecules in several human common viral infections, which would provide novel immune strategies for the prevention and treatment of human viral infection.

Role of interleukin-22 in the development and progression of liver fibrosis / 临床肝胆病杂志

Liver fibrosis is the result of persistent inflammatory response and chronic scar healing response during chronic liver injury and may progress to liver cirrhosis, portal hypertension, and liver failure, which finally requires liver transplantation. Interleukin-22 (IL-22) belongs to the IL-10 family and is the only cytokine that is produced by immune cells but does not act on immune cells. IL-22 plays a role by binding to its receptors IL-22R1 and IL-10R2, which has attracted much attention in the field of liver disease research in recent years. IL-22 not only plays the role of anti-inflammation and promotion of liver regeneration and tissue repair, but also has a pro-inflammatory effect in liver diseases, and it exerts a protective effect on the liver by reducing fibrosis in some pathological conditions, but there are still controversies over its association with liver fibrosis. IL-22 has different effects and mechanisms in liver fibrosis caused by different etiologies. This article reviews the role and possible mechanisms of IL-22 in liver fibrosis caused by viral infection (HBV and HCV), alcohol, high-fat diet, and autoimmunity.

Los niveles séricos de Interleucina 22 e Interleucina 6 disminuyen luego del tratamiento en pacientes con artritis reumatoidea / Interleukin 22 and Interleukin 6 Serum Levels Decrease After Treatment in Rheumatoid Arthritis Patients

Introducción: La artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: Se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR. Resultados: IL-22 e IL-6 fueron similares entre pacientes y controles. Sus niveles disminuyeron luego del tratamiento, principalmente en pacientes respondedores. IL-22 fue menor e IL-6 mayor en LS que en sangre. IL-6 correlacionó positivamente con PCR y anti-CCPhs. Los niveles de VSG, PCR y DAS28 fueron mayores en pacientes con valores dosables de IL-6 que en no dosables. Conclusión: En pacientes con valores basales dosables de IL-22 e IL-6, los niveles de estas citocinas podrían utilizarse como marcador adicional de respuesta al tratamiento.

Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.

Effect of mTORC1 on intestinal group 3 innate lymphocytes function / 上海交通大学学报（医学版）

Objective : To investigate the effect of mechanistic target of rapamycin complex 1 (mTORC1) on group 3 innate lymphoid cells (ILC3) function. Methods ¡¤ Intestinal lamina propria leukocytes (LPL) of C57BL/6 wild type mice were stimulated by rapamycin, the specific inhibitor of mTORC1 signaling pathway, in vitro, and then quantity and function of ILC3 were detected by flow cytometry. Next, purified ILC3 from mice intestinal LPL were sorted by flow cytometry. After the activation of ILC3 with IL-23, mRNA expression levels of Rorc (the gene encoding retinoic acid receptor related orphan receptor, i.e. RORγt), Il22 and Rptor (the gene encoding key component protein of mTORC1, i.e. Raptor) were detected by real-time qPCR. For further study, a genetically engineered mouse model specifically knocked out Raptor in ILC3 was constructed. Effects of mTORC1 loss on the quantity and function of ILC3 as well as gut structure were detected by flow cytometry, real-time qPCR and hematoxylin-eosin staining. Results ¡¤ The total ILC3 number had no change, but the secretion of IL-22 by ILC3 reduced after stim-ulation with rapamycin. Il22, Rorc and Rptor mRNA expression levels were upregulated simultaneously in ILC3 after activation with IL-23. In addition, there was no significant difference in the numbers and proportions of total ILC3 and ILC3 subsets as well as gut structure in Rap-tor-deficient mice, but the cytokine IL-22 secretion level of ILC3 significantly decreased in these mice. Conclusion ¡¤ Loss of mTORC1 func-tion inhibits ILC3 from secreting IL-22 but has no effect on the intestinal structure and intestinal ILC3 development, which reveals the positive regulation of mTORC1 signaling on intestinal ILC3 function.

Frequency changes of peripheral blood interleukin-22+CD4+CD161+ T cells in rheumatoid arthritis / 中华风湿病学杂志

Objective To analyze the frequency of interleukin (IL)-22+CD161+CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) patients compared with healthy control subjects and investigate the relationship of IL-22+CD4+CD161+ T lymphocyte frequency changes with RA disease activity.In addition to explore the pathogenesis of RA,and to look for new treatment targets for RA.Methods Twenty-one RA cases were included in the Department of Rheumatology of Tangshan Gongren Hospital from 2017 to 2018.Fourteen patients were female and 7 were male with the age ranged from 36 to 74 years old.The average age of this group of patients was (55±10) years,the average disease course was (60±50) months.All patients fulfilled the classification criteria of American College of Rheumatology [American College of Rheumatology (ACR)].Twenty-one subjects were enrolled as the control group,all of them came to Tangshan Gongren Hospital for regular health check-up.Fifteen subjects in the control group were female and 6 were male.Their age ranged between 40-78 years old with the average age of (55±9) years.IL-22+CD4+CD161+ T cells in PBMCs were detected by flow cytometry.The frequency variation of different CD4+CD161 + T was compared between case and control groups.The correlation was studied between the frequency and RA disease activity score (DAS28),tender joints number,swollen joints number,red blood cell sedimentation rate,high sensitive C reactive protein and white blood cell counts,red blood cell counts,platelet counts,IgG,IgA,IgM,complement C3 level,complement C4 level.T-test or Mann-Whitney U test were used for single-factor analysis,Pearson's test was used for correlation analysis.Results The percentage of RA group secreted CD4+ T cells (0.33± 0.20)％ of INF-γand IL-22,CD4+ T cells (0.51±0.29)％ of IL-22,and CD4+CD161+ T cells of IL-22 simultaneously.The number (0.55 ±0.28)％ was.significantly higher than that of the healtby control group [(0.22±0.14)％,(0.25±0.18)％,(0.36±0.24)％],and the differences were statistically significant [P=0.002,P=-0.0.45,P=0.026].Conclusion The percentage of IL-22+CD4+CD161+ T lymphocytes in the peripheral blood monocytes in RA patients is significantly higher than that in the healthy controls.The results of this study suggest that IL-22+CD4+CD161+ T lymphocytes in RA patients maybe related to RA disease activity and joint lesions.

Expression of serum neutrophil gelatinase-associated lipocalin in children with psoriasis and its pathogenic mechanisms / 中华皮肤科杂志

Objective@#To explore the relationships of neutrophil gelatinase-associated lipocalin (NGAL) with severity of skin lesions in children with psoriasis and peripheral neutrophil count, and to evaluate in vitro effect of NGAL on expression of tumor necrosis factor-α (TNF-α) and interleukin-22 (IL-22) by a human immortalized keratinocyte cell line HaCaT.@*Methods@#From January 1st 2017 to December 31st 2018, 98 children who newly developed psoriasis were enrolled from Department of Dermatology of 6 hospitals in China, including 51 males and 47 females. Their age was 7.00 ± 2.99 years (range: 3-14 years) , and their course of disease was 7.4 ± 5.85 days (range: 3-28 days) . The serum level of NGAL was detected in all the patients before and two weeks after treatment, and the relationships of NGAL with psoriasis area and severity index (PASI) scores and peripheral neutrophil count were evaluated. Western blot analysis and reverse-transcription (RT) -PCR were performed to determine the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells, respectively, after 12-hour treatment with NGAL at concentrations of 0 (control group) , 0.125, 0.25, 0.5, 1 mg/L. Statistical analysis was carried out with SPSS 16 software. by using t test and one-way analysis of variance.@*Results@#After 2-week treatment, the PASI score, neutrophil count and NGAL level in children with psoriasis significantly decreased (1.80 ± 1.19, [6.16 ± 0.76] × 109/L, 90.86 ± 0.75 μg/L, respectively) compared with those before the treatment (10.38 ± 3.42, [11.01 ± 2.85] × 109/L, 113.48 ± 21.26 μg/L, respectively; t = 31.42, 18.34, 16.37 respectively, all P < 0.001) . Before the treatment, the serum level of NGAL in the patients was positively correlated with the PASI score and peripheral neutrophil count (r = 0.918, 0.799 respectively, both P < 0.05) . The mRNA and protein expression of IL-22 in HaCaT cells significantly differed among these groups treated with different concentrations of NGAL (F = 176.31, 296.96 respectively, both P < 0.001) , so did the mRNA and protein expression of TNF-α (F = 193.28, 318.80 respectively, both P < 0.001) . Additionally, the protein and mRNA expression of IL-22 and TNF-α in HaCaT cells was significantly higher in the 0.125-, 0.25-, 0.5- and 1-mg/L NGAL group than in the control group (all P < 0.05) . The NGAL level was positively correlated with the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells (all P < 0.05) .@*Conclusions@#The serum level of NGAL was high in children with psoriasis, and positively correlated with severity of skin lesions and peripheral neutrophil count. NGAL can upregulate the expression of TNF-α and IL-22 in HaCaT cells in vitro.

Source analysis of lymphocytes secreting interleukin-22 from spleen of mice infected with Trichinella spiralis at the early encapsulated stage / 中华地方病学杂志

Objective To investigate the cell origin of interleukin (IL)-22-secreting cell of mice infected with Trichinella spiralis (T.spiralis) at the early encapsulated stage.Methods Twelve Balb/c mice were divided into the infected group and the control group according to body weight by random number table.The infected mice were intragastrically administrated with 300 muscle larvae of T.spiralis,and the control mice were given the same amount of normal saline.The IL-22-secreting cell subsets in mouse splenic lymphocytes were detected by flow cytometry at the fourth week after infection.Results The proportion of IL-22-secreting cells in splenic lymphocytes of T.spiralis infected mice was increased when compared with control group [(0.88 ± 0.25)％ vs (0.28 ±0.17)％,t =-4.899,P ＜ 0.05].There was no significant difference between the proportion of CD3+IL-22+ cells and CD3-IL-22+ cells in the splenic lymphocytes of the infected group [(0.29 ± 0.17)％ vs (0.51 ± 0.17)％,t =-2.195,P ＞ 0.05],and the percentage of CD3-IL-22+ cells were similar between the infected group and the control group [(0.51 ± 0.17)％ vs (0.44 ± 0.22)％,t =-0.600,P ＞ 0.05].The proportion of CD3+IL-22+ cells in the infected group was significantly higher than that in the control group [(0.29 ± 0.17)％ vs (0.07 ± 0.06)％,t =-3.068,P ＜ 0.05],and the percentage of CD4+IL-22+ T cells and γδTCR+IL-22+ T cells were obviously increased in CD3+ lymphocytes [(1.28 ± 0.54)％ vs (0.16 ± 0.07)％,(0.33 ± 0.22)％ vs (0.02 ± 0.00)％,t =-4.997,-3.342,P ＜ 0.05].Conclusions The proportion of IL-22-secreting splenic lymphocytes is increased in mice infected with T.spiralis at the early encapsulated stage.The rise is caused by increased numbers of IL-22-secreting CD3 + lymphocytes,especially CD4+ T cells and γδT cells.

Notch signaling pathway regulates IL-22 secretion by CD4+T cells in patients with Vogt-Koyanagi-Harada syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the changes of Notch receptors and interleukin(IL)-22 expression in patients with Vogt-Koyanagi-Harada(VKH)syndrome, and to assess the regulatory activity of Notch signaling to IL-22 production by CD4+ T cells in patients with VKH syndrome.<p>METHODS: Thirty-five patients with VKH syndrome(including fifteen active VKH and twenty inactive VKH)and twelve healthy controls were enrolled. Plasma was isolated, and CD4+T cells were purified. Notch receptors were investigated by qRT-PCR and Western blot. Plasma IL-22 expression was measured by ELISA. The percentage of Th17 and Th22 cells was investigated by flow cytometry. CD4+T cells, which were purified from active VKH patients, were stimulated with Notch signaling inhibitor DAPT. mRNA expression of transcription factor in CD4+T cells as well as IL-22 secretion by CD4+T cells was investigated.<p>RESULTS: Notch1-Notch3 in CD4+T cells from active VKH syndrome patients was significantly elevated in comparison with inactive VKH and healthy controls. Plasma IL-22 expression and percentage of Th17 and Th22 was notably increased in active VKH syndrome in comparison with inactive VKH and controls. DAPT stimulation inhibited Notch signaling pathway in CD4+T cells, leading to the down-regulation of AhR mRNA and IL-22 secretion.<p>CONCLUSION:Notch-AhR-IL-22 signaling pathway might take part in the pathogenesis of VKH syndrome.

Carbohydrate and lipid disorders and adipokines levels in relation to body mass index in hypertensive patients / Trastorno del metabolismo de carbohidratos y lípidos y los niveles de adipoquinas en relación con el índice de masa corporal en pacientes con hipertensión

Abstract: Obesity is considered as a valid risk factor for cardiovascular disease, due to the fact that the risk of morbidity and mortality from various causes in obese people is significantly higher. Exact mechanisms of metabolic disorders in hypertension with obesity is still discussible. The aim of the study - to determine the peculiarities of carbohydrate, lipid metabolism changes and activity of adipokines and interleukin-22, in patients with hypertension according to nutritional status. Methods: 80 patients (37 males and 43 females) with essential hypertension (EH) of average age 60.17 years were examined. Carbohydrate, lipid profiles, apolipoprotein B (apo B), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), adiponectin, interleukin-22 (IL-22) were estimated. Results: In patients with EH and obesity was found carbohydrates metabolism abnormalities, that was manifested as hyperinsulinemia, glucose and HbA1c levels elevation and insulin resistance (according to HOMA index). Lipid metabolism disorders were observed as valid increasing of triglycerides and apo B. Body mass index elevation was associated with progressive increasing of TNF-α and PAI-1 concentration with reducing of adiponectin level in the patients with EH. Positive relationships between TNF- and HbA1c, apo B; PAI-1 with glucose levels: negative correlation adiponectin with body mass and waist to hip ratio were detected in the patients with obesity associated (BMI ≥ 30 kg/m2) EH. Positive significant correlations between apo B and insulin levels, HOMA index, and TNF-α concentration were defined. IL-22 in overweigh and obese patients was significantly higher, correlates negatively with HDL-C. Conclusion: In patients with EH and obesity the adipokine dysfunction was revealed, that correlates with carbohydrate and lipid parameters that indicate increased proinflammatory and prothrombogenic processes.(AU)

Resumen: La obesidad se considera un factor de riesgo válido para las enfermedades cardiovasculares, debido a que el riesgo de morbilidad y mortalidad por diversas causas en personas obesas es significativamente mayor. Los mecanismos exactos de los trastornos metabólicos en la hipertensión con obesidad todavía son discutibles. El objetivo del estudio - determinar las peculiaridades de los carbohidratos, los cambios en el metabolismo de los lípidos y la actividad de las adipoquinas y la interleucina 22, en pacientes con hipertensión según el estado nutricional. Métodos: Se examinaron 80 pacientes (37 hombres y 43 mujeres) con hipertensión esencial (HE) de edad promedio de 60.17 años. Se estimaron los perfiles de carbohidratos, lípidos, apolipoproteína B (apo B), factor de necrosis tumoral-α (TNF-α), inhibidor activador del plasminógeno-1 (PAI-1), adiponectina, interleucina-22 (IL-22). Resultados: En pacientes con HE y obesidad se encontraron anomalías en el metabolismo de los carbohidratos, que se manifestaron como hiperinsulinemia, elevación de los niveles de glucosa y HbA1c y resistencia a la insulina (según el índice HOMA). Se observaron trastornos del metabolismo de los lípidos como aumento válido de triglicéridos y apo B. La elevación del índice de masa corporal se asoció con el aumento progresivo de la concentración de TNF-α y PAI-1 con la reducción del nivel de adiponectina en los pacientes con HE. Relaciones positivas entre TNF- y HbA1c, apo B; PAI-1 con niveles de glucosa: se detectaron correlaciones negativas de adiponectina con masa corporal y relación cintura-cadera en los pacientes con obesidad (IMC ≥ kg/m2) asociada con HE. Se definieron correlaciones positivas significativas entre los niveles de apo B e insulina, el índice HOMA y la concentración de TNF-α. La IL-22 en pacientes con sobrepeso y obesos fue significativamente mayor, se correlaciona negativamente con HDL-C. Conclusión: En pacientes con HE y obesidad se reveló la disfunción de la adipoquina, que se correlaciona con parámetros de carbohidratos y lípidos que indican un aumento de los procesos proinflamatorios y protrombogénicos.(AU)

The mechanism of interleukin-22 induced the secretion of vascular endothelial growth factor A in gastric cancer cell line AGS / 国际检验医学杂志

Objective To investigate the mechanism of interleukin-22(IL-22) induced the secretion of vas-cular endothelial growth factor A(VEGF-A) in gastric cancer cell line AGS .Methods Gastric cancer cell line AGS were cultured in vitro ,and recombination cytokine IL-22 were added ,or signal pathway inhibitor were pre-incubated with AGS for 1 hour and then IL-22 were added ,the level of VEGF-A were detected by enzyme-linked immunosorbent assay .Results Compared with the unstimulated group ,the secretion of VEGF-A in IL-22-stimulated group was significantly increased ,the difference was statistically significant (P＜0 .05) ,which was in a dose and time dependent manner .In addition ,IL-22-stimulated the secretion of VEGF-A by AGS was significantly decreased while pre-incubated by the signal transducers and activators of transcription 3(STAT3) inhibitor ,the difference was statistically significant (P＜0 .05) ,but such effect was not observed while AGS were pre-incubated with the nuclear factor kappa B inhibitor ,c-Jun N-terminal kinase inhibitor ,mitogen-acti-vated protein kinase kinase 1/2 inhibitor and p38 mitogen-activated protein kinase inhibitor ,there was no sta-tistical significance(P＞0 .05) .Conclusion IL-22 could induce the secretion of VEGF-A in gastric cancer cell line AGS via STAT3 signal pathway ,which may contribute to tumor progression .

Distribution characteristics of polymorphisms of interleukin-22 gene in Guangxi population and their association with serum lipid levels / 中国病理生理杂志

AIM:To investigate the distribution characteristics of interleukin-22(IL-22)gene rs2227485C/T and rs2227491A/G polymorphisms in Guangxi people and the distribution differences with other ethnic groups ,and to ex-plore the difference levels of common lipid indexes in different genotypes.METHODS:SNaPshot technique and DNA se-quencing were used in 280 Guangxi persons to examine IL-22 genotypes and to analyzed the distribution frequencies of allele and genotype in these sites.The distribution frequencies in different sexes ,and the differences between groups and diffe-rence levels of common lipid indexes in different genotypes were analyzed statistically.RESULTS:Three genotypes of CC ,CT and TT were found in rs2227485C/T with the frequency distribution of 17.1％,49.3％and 33.6％,respectively.No significant difference between different sexes of each genotype and allele frequency in the Guangxi population was observed(P>0.05).Compared with the distribution frequencies of genotype and allele in HapMap -TSI,HapMap-HCB,HapMap-JPT and HapMap-MEX,those in Guangxi population showed statistically significant differences(P<0.05).Three geno-types of AA,AG and GG were found in rs2227491A/G with the frequency distribution of 16.1％,52.8％and 31.1％,re-spectively.There was no significant difference between different sexes of each genotype and allele frequency in the Guangxi population(P>0.05).The significant differences of genotype frequencies among Guangxi population ,HapMap-TSI,Hap- Map-JPT and HapMap-MEX were detected(P <0.05 ).Compared with the other 4 populations ,allele frequencies in Guangxi population had significant difference(P <0.05).There were significant differences in the levels of HDL-C and LDL-C among the 3 genotypes of rs2227491A/G.The level of HDL-C had difference between AG/AA genotype and GG genotype.In addition,the level of LDL-C had difference between AG/GG genotype and AA genotype(P<0.05).CON-CLUSION:rs2227485C/T and rs2227491A/G polymorphisms of IL-22 gene have differences in different populations.The rs2227491A/G polymorphism may be associated with serum lipid levels.

Clinical Significance of Th22 Cells in Assessing the Severity and Prognosis of Patients with Sepsis / 医学研究杂志

Objective To investigate the clinical significance of peripheral blood T-helper (Th22) cells in assessing the severity and prognosis of patients with sepsis.Methods A total of 220 patients with sepsis in our hospital from January 2013 to January 2017 were enrolled in the study.According to the severity of sepsis,these patients were divided into low risk group (84 cases),middle risk group (74 cases) and high risk group (62 cases).According to the clinical outcome of sepsis,these patients were divided into survival group (195 cases) and death group (25 cases).The levels of Th22 cells,IL-22 and CRP in the peripheral blood were measured,and the acute physiology and chronic health status (APACHE Ⅱ) score were recorded,the predictive value of peripheral blood Th22 cells in deathof sepsis was assessed by the receiver operating characteristic curve (ROC).Results The levels of Th22 cells,IL-22 and APACHE Ⅱ in the low-risk group,the intermediate-risk group and the high-risk group were statistically significant (P ＜ 0.05).The high-risk group was highest,followed by the intermediate-risk group,the low-risk group was lowest among them.The levels of Th22,IL-22 and APACHE Ⅱ scores of the death group were significantly higher than those in the survival group (P ＜ 0.05).The correlation analysis showed that the Th22 celss in peripheral blood were positively correlated with IL-22 (r =0.70,P ＜ 0.01) and APACHE Ⅱ scores (r =0.75,P ＜ 0.01).When Th22 cells in peripheral blood ＞ 3.3％ for the assessing the poor prognosis of sepsis boundaries,the sensitivity and specificity were 84.4％ and 86.1％.Conclusion The Th22 cells in peripheral blood and IL-22 are closely related to the severity and prognosis of sepsis,serving as an assessing index and have important clinical value.

Expression and Significance of IL-22BP in Intestinal Mucosa of Patients With Active Inflammatory Bowel Disease / 胃肠病学

Background:As the endogenous inhibitor of interleukin(IL)-22,IL-22 binding protein(IL-22BP)inhibits the protective effect of IL-22. Expression and significance of IL-22BP in intestinal mucosa of patients with active inflammatory bowel disease(IBD)remain unclear. Aims:To investigate the expression and significance of IL-22BP in intestinal mucosa of patients with active IBD. Methods:A total of 25 Crohn's disease(CD)and 36 ulcerative colitis(UC)patients from Jan. 2017 to Jan. 2018 at Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine were enrolled, and 30 colonic polyp patients were served as controls. The disease activity of CD and UC was assessed. Expressions of IL-22BP mRNA and protein in intestinal mucosa were determined by real-time fluorescent quantitative PCR and immunohistochemistry,respectively. Correlation of IL-22BP protein expression with the disease activity of CD,UC was analyzed. Results:Compared with corresponding control group,expressions of IL-22BP mRNA in intestinal mucosa in CD and UC groups were significantly increased(CD:3.59 ± 0.83 vs. 1.08 ± 0.45,P<0.001;UC:2.19 ± 0.52 vs. 1.05 ± 0.34,P<0.001),and expressions of IL-22BP protein were also significantly increased(CD:6.12 ± 2.30 vs. 1.83 ± 1.86,P<0.001;UC:5.58 ± 2.27 vs. 2.23 ± 1.77,P<0.001). Expression of IL-22BP protein in intestinal mucosa was positively correlated with disease activity of CD(r =0. 649,P <0. 001)and UC(r =0. 732,P <0.001). Conclusions:Expressions of IL-22BP mRNA and protein are increased in intestinal mucosa of patients with active IBD, and the expression of IL-22BP protein is positively correlated with disease activity of IBD.

Distribution of Interleukin-22–secreting Immune Cells in Conjunctival Associated Lymphoid Tissue

PURPOSE: Interleukin (IL)-22 is a cytokine involved in epithelial cell regeneration. Currently, no research studies have analyzed the distribution of the three distinct IL-22–secreting cell populations in human or mouse conjunctiva. This study investigated the distribution of the three main populations of IL-22–secreting immune cells, αβ Th cells, γδ T cells, or innate cells (innate lymphoid cells [ILCs] or natural killer cells), in conjunctival associated lymphoid tissues (CALTs) in human and mouse models. METHODS: We collected discarded cadaveric bulbar conjunctival tissue specimens after preservation of the corneo-limbal tissue for keratoplasty from four enucleated eyes of the domestic donor. The bulbar conjunctiva tissue, including the cornea from normal (n = 27) or abraded (n = 4) B6 mice, were excised and pooled in RPMI 1640 media. After the lymphoid cells were gated in forward and side scattering, the αβ Th cells, γδ T cells, or innate lymphoid cells were positively or negatively gated using anti-CD3, anti-γδ TCR, and anti–IL-22 antibodies, with a FACSCanto flow cytometer. RESULTS: In normal human conjunctiva, the percentage and number of cells were highest in αβ Th cells, followed by γδ T cells and CD3–γδ TCR – IL-22+ innate cells (presumed ILCs, pILCs) (Kruskal-Wallis test, p = 0.012). In normal mice keratoconjunctiva, the percentage and total number were highest in γδ T cells, followed by αβ Th cells and pILCs (Kruskal-Wallis test, p = 0.0004); in corneal abraded mice, the population of αβ Th cells and pILCs tended to increase. CONCLUSIONS: This study suggests that three distinctive populations of IL-22–secreting immune cells are present in CALTs of both humans and mice, and the proportions of IL-22+αβ Th cells, γδ T cells, and pILCs in CALTs in humans might be differently distributed from those in normal mice.

IL-22 alleviates hydrogen peroxide-induced hepatocarcinoma cell damage through activating autoph-agy / 中华微生物学和免疫学杂志

Objective To investigate the role of interleukin-22 (IL-22)-regulated autophagy in hydrogen peroxide (H2 O2 )-induced hepatocarcinoma cell damage. Methods HepG2 cells were transfected with pEGFP-LC3 and then cultured in RPMI 1640 medium free of fetal bovine serum (FBS) or containing 1％ or 10％ FBS. These cells were pretreated with rapamycin or an autophagy inhibitor (3-MA) and then stimulated with recombinat human IL-22 (rhIL-22). GFP-LC3 puncta formation and autophagy signaling ac-tivation were measured. MTT assay was performed to detect cell viability. Results rhIL-22 significantly promoted GFP-LC3 puncta formation and LC3-Ⅱ expression in HepG2 cells treated with different stimulation protocols. The autophagy pathway inhibitor, 3-MA, dramatically suppressed the rhIL-22-activated autophagy signals. rhIL-22 attenuated H2 O2-mediated HepG2 cell death and that could be inhibited by 3-MA. Conclu-sion IL-22 promoted the activation of autophagy signaling pathways and alleviated H2 O2-mediated HepG2 cell damage.

Effects of interleukin-22 on the expression of CC chemokine ligand 27 in human epidermal keratinocytes / 中华皮肤科杂志

Objective To evaluate the effects of interleukin-22 (IL-22) on the expression of CC chemokine ligand 27 (CCL27) in human epidermal keratinocytes,and to explore its mechanism.Methods Immunohistochemical study was performed to determine the expression of CCL27 in skin lesions of 10 patients with psoriasis and skin tissues of 5 healthy controls.Cultured HaCaT cells were divided into 8 groups:control group treated with PBS,5 IL-22 groups treated with 12.5,25,50,100 and 200 μg/L IL-22 respectively,2 signaling pathway inhibition groups treated with 50 μrmol/L AG490 (JAK2/STAT3 signaling pathway inhibitor) or PD98059 (MAPK-ERK1/2 signaling pathway inhibitor) for 2 hours followed by the treatment with 50 μg/L IL-22 in the 5％ CO2 incubator at 37 ℃.After 24-hour cultivation,total proteins were extracted,and culture supernatants were collected,and both Western blot analysis and enzyme-linked immunosorbent assay (ELISA) were performed to determine the expression of CCL27.Results Immunohistochemical study showed that the expression of CCL27 was significantly higher in the skin lesions of the patients with psoriasis than in the skin tissues of the healthy controls.Western blot analysis revealed that the protein expression of CCL27 in the 12.5-,25-,50-,100-and 200-μg/L IL-22 groups was 0.491 ± 0.013,0.620 ± 0.019,0.623 ± 0.014,0.802 ± 0.052 and 1.138 ± 0.013 respectively,which were all higher than that in the control group (0.413 ± 0.013,all P ＜ 0.01).The expression of CCL27 was significantly lower in the IL-22 + AG490 group (0.411 ± 0.019) and IL-22 + PD98059 group (0.280 ± 0.012) than in the 50-μg/L IL-22 group (both P ＜ 0.01).ELISA also showed the same trend of changes in the level of CCL27 in the above groups as Western blot showed.Conclusion IL-22 can promote the expression of CCL27 in HaCaT cells,which may be associated with the MAPK-ERK 1/2 and JAK2/STAT3 signaling pathways.