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.

Huangkui capsule in combination with leflunomide improves immunoglobulin a nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway.

OBJECTIVES: To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN) METHODS: IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining. RESULTS: Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001). CONCLUSIONS: By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.

Change and significance of HBcAg-specific Th22 cells in patients with hepatitis B virus infection / 临床肝胆病杂志

ObjectiveTo investigate the changes of Th22 cells, interleukin-22 (IL-22), and transcription factor aryl hydrocarbon receptor (AhR) in patients with hepatitis B virus (HBV) infection and their correlation with clinical indices. MethodsA total of 11 patients with acute hepatitis B (AHB) and 38 patients with chronic hepatitis B (CHB) who attended Eighth Hospital of Xi’an from March 2018 to March 2019 were enrolled as AHB group and CHB group, respectively, and 16 healthy controls were enrolled as HC group. The patients with CHB received tenofovir disoproxil fumarate (TDF) antiviral therapy. Peripheral blood samples were collected for AHB patients at baseline and 6 months after discharge, and peripheral blood samples were collected for CHB patients at baseline and at months 6 and 12 of treatment; peripheral blood mononuclear cells (PBMCs) and plasma were isolated, then PBMCs were stimulated with phorbol ester+ionomycin or recombinant HBcAg, and flow cytometry was used to measure nonspecific CD3+CD4+IL-22+ Th22 cells and HBcAg-specific Th22 cells. ELISA was used to measure the plasma level of IL-22, and quantitative real-time PCR was used to measure the mRNA expression of AhR in PBMCs. The t-test and the paired t-test were used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to investigate correlation. ResultsThe AHB group had a significantly higher percentage of nonspecific Th22 cells than the CHB group (2.86%±0.45% vs 1.39%±0.33%, t=11.80, P＜0.001) and the HC group (2.86%±0.45% vs 0.80%±0.13%, t=17.30, P＜0.001), and the CHB group also had a significantly higher percentage of nonspecific Th22 cells than the HC group (t=6.825, P＜0.001). The AHB group had a significantly higher percentage of HBcAg-specific Th22 cells than the CHB group (2.97%±0.52% vs 1.22%±0.22%, t=16.58, P＜0.001). The AHB group had a significantly higher plasma level of IL-22 than the CHB group (130.7±39.97 pg/ml vs 66.59±20.83 pg/ml, t=7.176, P＜0.001) and the HC group (130.7±39.97 pg/ml vs 50.63±11.07 pg/ml, t=7.662, P＜0.001), and the CHB group also had a significantly higher plasma level of IL-22 than the HC group (t=2.887, P=0.006). The AHB group had significantly higher mRNA expression of AhR than the CHB group (11.45±3.03 vs 4.81±125, t=10.85, P＜0.0001) and the HC group (11.45±3.03 vs 1.10±0.17, t=13.75, P＜0.001), and the CHB group also had significantly higher mRNA expression of AhR than the HC group (t=11.77, P＜0.001). In both AHB and CHB patients, the percentage of HBcAg-specific Th22 cells was positively correlated with alanine aminotransferase (ALT) level (r=0.638 and 0.830, P=0035 and 0002), and the plasma level of IL-22 was also positively correlated with ALT level (r=0.552 and 0.431, P=0.001 and 0.007). The AHB patients were followed up at 6 months after discharge, and there were significant reductions in the percentage of HBcAg-specific Th22 cells (2.79%±0.56%, t=3.055, P=0.012) and the plasma level of IL-22 (105.8±25.23 pg/ml, t=2.362, P=0.040) from baseline. All CHB patients received TDF antiviral therapy and were followed up at months 6 and 12 of treatment, and there were significant reductions in the percentage of HBcAg-specific Th22 cells (t=4.353 and 3.927, all P＜0.001) and the plasma level of IL-22 (t=4426 and 4.810, both P＜0.0001) from baseline to months 6 and 12 of treatment. ConclusionHBcAg-specific Th22 cells and IL-22 are closely associated with inflammatory response to HBV infection.

Role of Th22 cells and cytokine interlukin 22 secreted by Th22 in breast cancer / 中国医师进修杂志

Objective To investigate the role of Th22 cells and interlukin 22(IL-22) secreted by Th22 cells in the development of breast cancer. Methods The breast cancer model was established by in situ inoculation of 4T1 breast cancer cells in mice. The experimental group (20 cases) was injected with phosphoric acid buffer (PBS) 0.1 ml containing 4105 4T1 cells into the breast fat pad of mice, while the control group (20 cases) was injected with PBS 0.1 ml into the breast fat pad of mice without cells. Flow cytometry was used to detect Th22 cells in peripheral blood and enzyme linked immunosorbent assay (ELISA) was used to detect the level of IL-22 in serum. The difference of IL-22 levels between Th22 cells and serum was compared between the two groups, and the correlation between Th22 cells and IL-22 was analyzed. Real-time fluorescence quantitative PCR was used to detect the expression of IL-22. The phosphorylation of STAT3 in 4T1 cells treated with IL-22 was detected by Western blot. Results Tumors grew one week after in situ inoculation, and the expression of Th22 cells and IL-22 in serum was significantly increased and positively correlated with that in control group (r＝0.569, P＜0.01 or ＜0.05). The level of IL-22 mRNA in tumor group was significantly increased compared with that in normal group:(22.28 ± 2.52) ng/L vs. (18.92 ± 1.80) ng/L (P＜0.01), and STAT3 was phosphorylated by 4T1 cells after IL-22 treatment. Conclusions Th22 cells and cytokines IL-22 secreted by them can promote the occurrence and development of breast cancer by affecting STAT3 phosphorylation.

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.

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.

From Bench to Clinic: the Potential of Therapeutic Targeting of the IL-22 Signaling Pathway in Atopic Dermatitis

Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.

Study on role of Th22 cells and its functional cytokine IL-22 in lupus nephritis / 中国免疫学杂志

Objective:To observe the expressions of Th22 cells and IL-22 in peripheral blood of patients with Lupus nephritis (LN) and explore its significance.Methods: Patients of systemic lupus erythematosus (SLE) with no renal involvement (n=38),lupus nephritis (n=32) and healthy controls (n=10) were studied.Flow cytometry was utilized to quantify the percentage of Th22 cells in peripheral blood.Enzyme-linked immunosorbent assay was used to detect the levels of serum IL-22.The Th22 cells and The serum level of IL-22 among three groups were compared,and the correlation between Th22,IL-22 and SLE disease activity index score (SLEDAI) was analyzed.Results: Th22 cells in SLE group and LN group were significantly higher than those in healthy control group (P0.05).The proportion of Th22 cells and the level of IL-22 in LN group were positively correlated with the disease activity score SLEDAI.Conclusion: Th22 cells and IL-22 may play an important role in the pathogenesis of SLE and LN.

Frequency of Th22 cells and expression of their related cytokines in peripheral blood of patients with alopecia areata and their significance / 中华皮肤科杂志

Objective To determine the frequency of Th22 cells and expression of their related cytokines in peripheral blood of patients with alopecia areata(AA), to investigate their significance, and to explore the role of T lymphocytes in the occurrence of AA. Methods A total of 38 patients with AA were enrolled from Central Hospital of Minhang District in Shanghai between January 2015 and May 2016, and served as the case group. At the same time, 38 healthy people served as the control group. Peripheral blood samples were obtained from these patients and controls. Flow cytometry was performed to determine the percentage of Th22 cells, and enzyme?linked immunosorbent assay(ELISA)to measure serum levels of interleukin?22(IL?22)and IL?17. Results Compared with the control group, the case group showed significantly increased percentages of Th22 cells, Th17 cells, IL?17+IL?22+CD4+T cells and IFN?γ+IL?22+CD4+ T cells(all P < 0.01), as well as serum levels of IL?22 and IL?17(both P < 0.05). A significant increase was observed in percentages of Th22 cells, Th17 cells, IL?17+IL?22+CD4+T cells and IFN?γ+IL?22+CD4+T cells, as well as serum levels of IL?22 and IL?17, in patients with severe AA compared with those with mild AA, and in patients with active AA compared with those with stable AA (all P < 0.05). Conclusion Th22 cells and their related cytokines may participate in the occurrence, development and prognosis of AA.

Changes and significance of peripheral blood Th22 level in patients with sepsis / 重庆医学

Objective To investigate the change of peripheral blood Th22 cells level in the patients with sepsis and its clinical significance .Methods A total of 180 patients with sepsis in this hospital from April 2014 to April 2017 were selected as the re-search subjects and divided into the common sepsis group (81 cases) ,severe sepsis group (68 cases) and septic shock group (31 ca-ses) according to the sepsis severity .The levels of IL-22 ,IL-6 and PCT in peripheral blood Th22 cells were measured in each group .The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores were recorded .The efficiency of peripheral blood Th22 cells in the early diagnosis of sepsis was evaluated by adopting the receiver operating characteristic (ROC) curve .Results The levels of peripheral blood Th22 cells and IL-22 in the patients with sepsis were significantly than those in the control group (P<0 .05) .The levels of Th22 cells ,IL-22 and PCT and APACHE Ⅱ scores had statistical differences among the common sepsis group ,severe sepsis group and septic shock group (P<0 .05) .The correlation analysis showed that peripheral blood Th22 cells lev-el was positively correlated with PCT level and APACHE Ⅱ scores respectively (r=0 .80 ,0 .66 ,P<0 .01) .With peripheral blood Th22 cells level=1 .9% as the boundary for early diagnosis of sepsis ,its sensitivity and specificity were 83 .1% and 85 .2% respec-tively ,which was significantly better than the PCT index .Conclusion Peripheral blood Th22 cells and related cytokines have the important clinical application value for the early diagnosis of sepsis and assessment of disease severity .

Clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis / 中华肝脏病杂志

Objective@#To investigate the clinical features of imbalance between Th1 and Th22 cells and its association with disease progression in patients with liver cirrhosis, and to explore immune therapeutic strategies for targeted therapy for liver cirrhosis.@*Methods@#In vitro peripheral blood mononucleated cells (PBMCs) were collected by centrifugation. CD3-BV500 and CD8-PerCP-Cy5.5 staining was performed for these cells. IFNγ-PE-Cy7, IL-17a-APC, IL-22-PE, or the corresponding isotype control was added, and then PBMCs were fixed with 1% polyoxymethylene after being washed once by permeabilization-wash buffer. Flowjo software was used for the analysis of T lymphocyte subsets and cytokines. Th1 (CD4+IFNγ+), Th17 (CD4+IL-17a+), Th22 (CD4+IL-22+), Tc1 (CD8+IFNγ+), Tc17 (CD8+IL-17a+), and Tc22 (CD8+IL-22+) subsets were defined and the secretions of interferon-γ (IFN-γ), interleukin-17a (IL-17a), and interleukin-22 (IL-22) were measured for all subsets. LX-2 cells were cultured in a serum-free medium and different concentrations of recombinant human IL-22 protein (25, 50, 100 ng/ml) were added; 24 hours later, the activation marker α-smooth muscle actin (α-SMA) was used to measure LX-2 activation. Fetal bovine serum with a volume fraction of 10% was used as a positive control. Enzyme-linked immunosorbent assay (chemiluminescence) was used to measure the concentrations of hyaluronic acid, type III precollagen, and type IV collagen in supernatant. A one-way analysis of variance, the non-parametric Mann-Whitney U test, and the non-parametric Kruskal-wallis H test were used for statistical analysis based on data type.@*Results@#Compared with the health control group, the liver cirrhosis groups with various causes had significant increases in peripheral Tc1, Th17, and Th22 cells. The percentage of Th17 cells in the liver cirrhosis group was 1.64 times that in the control group (4.25%±2.45% vs 2.59%±1.36%, P < 0.05), and the mean percentage of Th22 cells in the liver cirrhosis group was 2.18 times that in the control group (4.17%±2.55% vs 1.31%±0.64%, P < 0.05). The percentages of Th17 (5.89%±3.44%) and Th22 cells (5.32%±3.67%) in the patients with alcoholic cirrhosis were 1.27 and 3.06 times those in the control group (P < 0.05). The patients with alcoholic cirrhosis had a significant increase in Th22 cells. The patients with different types of liver cirrhosis had a significant reduction in the ratio between anti-fibrotic and pro-fibrotic factors (Th1/Th22), which was positively correlated with the severity of liver cirrhosis and was a common immunological feature of liver cirrhosis with different causes. In addition, IL-22 activated hepatic stellate cells and promoted the production of collagen.@*Conclusion@#The imbalance between anti-fibrotic and pro-fibrotic factors (Th1/Th22) is a common feature of the progression of liver fibrosis with various causes and may contribute to the progression of liver fibrosis.

Change of Th2 2 Cells in Peripheral Blood of Patients with Primary Sj ogren’s Syndrome and Clinical Significance / 现代检验医学杂志

Objective To investigate the change of Th22 cells in peripheral blood of patients with Primary sjogren’s syndrome (pSS)and evaluate clinical significance.Methods 37 patients with pSS from January 2014 to November 2015 were enrolled the study as the observation group.Then 37 healthy adults receiving check-up during the same period were selected as con-trol groups in accordance with the proportion of 1∶1.Flow cytometry was performed to evaluate the levels of Th22 cells in peripheral blood,and tenzyme-linked immuno sorbent assay (ELISA)was used to measure the serum IL-22 levels.Pearson analysis was performed to investigate the relationship between Th22 level and serum IL-22 level,C3,C4,anti-SSA,anti-SSB, ANA antibody,EULAR Sjogren's syndrome disease activity index (ESSDAI)score in observation group.Then the levels of Th22 cells and serum IL-22 were compared among different labial gland pathologic stage in patients with pSS.Results The levels of Th22 cells and serum IL-22 in the observation group were (2.53±1.56)%,718.6±176.8 pg/ml respectively,and significantly higher than (1.24±0.51)%,258.9±72.4 pg/ml in control group (P0.05).Conclusion The levels of Th22 cells and serum IL-22 significantly in-creased in patients with pSS,and related to other inflammatory indexes and disease activity,so they may participate in the genesis and development of pSS.

Changes in serum levels of Th22 cell-related cytokines and complements in patients with drug eruption before and after treatment / 中华皮肤科杂志

Objective To investigate changes in serum levels of Th22 cell ? related cytokines and complements in patients with drug eruption before and after treatment, and to explore their possible roles in the occurrence and development of drug eruption. Methods This study included 35 patients with drug eruption, and 35 sex?and age?matched healthy controls. Five milliliters of peripheral blood samples were collected from the controls and patients before and after treatment. Enzyme?linked immunosorbent assay(ELISA)was performed to measure serum levels of interleukin 22(IL?22)and IL?13, and the cytometric bead array(CBA)system was used to determine serum levels of tumor necrosis factor?α(TNF?α) and complement components C3a, C4a and C5a. Results Before treatment, the patients with drug eruption showed significantly higher serum levels of IL?22(40.85 ± 14.56 vs. 29.09 ± 8.66 ng/L, t=5.549, P 0.05). Correlation analysis showed positive correlations between complement C3a and C4a serum levels(r = 0.660, P < 0.05), between C3a and C5a serum levels(r = 0.404, P < 0.05), between C4a and C5a serum levels(r = 0.501, P < 0.05), and between IL ? 22 and TNF ? α serum levels(r = 0.573, P = 0.005), but negative correlations between IL ? 22 and complement C3a serum levels(r = -0.490, P = 0.005), in patients before treatment. Conclusion The activation of Th22 cell?related cytokines and complements may play important roles in the occurrence and development of drug eruption, and IL?22 may participate in the regulation of complements.

Dynamic Changes of Type Th22 Cell Immunological Response During Atherosclerosis Process in Experimental Mice / 中国循环杂志

Objective: To study the dynamic changes of type Th22 cell immunological response during atherosclerosis process in experimental mice in order to provide a new theoretical basis for atherosclerosis therapy. Methods: 8 weeks C57BL/6J mice were divided into 2 groups: Experiment group,n=24 ApoE-/- mice and Control group, n=24 normal mice. All animals received high fat diet and the following indexes were compared between 2 groups at 0, 4, 8, 12 weeks after treatment: aortic atherosclerotic lesions were deifned by Oil red O staining, dynamic changes of Th22 cells in spleen were measured by lfow cytometry, mRNA expressions of interleukin-22 (IL-22), IL-22R1, AhR and T-bet in aorta were examined by RT-PCR, blood levels of IL-22 was detected by ELISA. Results: Compared with Control group, Experiment group had the increased area of aortic atherosclerosis (the ratio of plaque area/lumen area) and Th22 cell (CD4+ IL-22+/CD4+T cell) amount, elevated mRNA expressions of IL-22, IL-22R1, AHR, T-bet in aorta and higher blood levels of IL-22 at all time points, the differences between each time point (except 0 week) had the statistic meaning,P<0.05. In Experiment group, the differences between 2 adjacent time points, for the area of aortic atherosclerosis and mRNA expressions of AHR, T-bet: 4 weeks vs 0 week, 8 weeks vs 4 weeks, 12 weeks vs 8 weeks all had statistic meaning; for Th22 cell amount: 4 weeks vs 0 week, 8 weeks vs 4 weeks had statistic meaning and 12 weeks vs 8 weeks had no real distinction; for mRNA expressions of IL-22, IL-22R1 and blood levels of IL-22: 4 weeks vs 0 week had statistic meaning and 8 weeks vs 4 weeks, 12 weeks vs 8 weeks had no real distinctions. Conclusion: Hyperactive immunological response of Th22 cells might be involved in atherosclerosis process, the relevant mechanism should be further studied.

Variation and significance of helper T cells and regulatory T cells in the peripheral blood before and after antiretroviral treatment of human immunodeficiency virus-1 infected patients / 中华传染病杂志

Objective To investigate the changes and clinical significance of helper T cells (Th)22,Th17,Th1 and regulatory T cells (Treg) in the peripheral blood before and after antiretroviral treatment (ART) of human immunodeficiency virus (HIV)-1 infected patients.Methods Forty HIV-infected patients were recruited into this study,and 30 healthy subjects were recruited as controls.Peripheral blood of the patients was collected at baseline and after 3 months of ART treatment.The frequencies of Th22,Th17,Th1 and Treg were detected by flow cytometry.Tests for homogeneity of variance and paired t test for comparison was adopted.Spearman rank test was used for correlation analysis.Results The frequencies of peripheral Th22,Th17,Th1 and Treg from HIV-infected patients before treatment were significantly decreased compared to the healthy controls ([0.59± 0.47] ％ vs [1.65 ± 0.56] ％ [t =8.544,P＜0.01],[4.46±1.84]％ vs [6.98±1.86]％[t=5.619,P＜0.01],and [16.75±6.72]％ vs [22.77±6.87]％; [t=5.311,P＜0.01].The frequencies of peripheral Th22 and Th17 after 3 months of treatment were significantly higher than those at baseline ([1.60± 1.10] ％ [t=5.268,P＜0.01] and [6.33±2.64]％ [t=3.663,P＜0.01] and no difference from those of healthy controls (t=1.783 and 1.143,respectively; both P＞0.05).However,the Th1 frequency showed no difference compared to the baseline.The frequency of Treg in the HIV infected patients was significantly increased compared with the healthy controls ([10.76±3.76]％ vs [7.01±1.88]％,t=5.003,P＜0.01).However,it gradually decreased along with the ART treatment ([9.22±2.56]％ after 2 months; [8.57± 2.36]％ after 3 months),which was still higher than that of healthy controls (t=2.984,P=0.004).The ratios of Th22/Treg,Th17/Treg and Th1/Treg of the HIV-infected patients were significantly decreased in comparison with the healthy controls (0.05±0.03 vs 0.25±0.10,t=11.69,P＜0.01; 0.46 ± 0.27 vs 1.07±0.42,t=7.728,P＜0.01; 1.56±0.89 vs 3.37± 1.02,t=7.052,P＜0.01),and those were significantly increased after 3 months of treatment (0.17±0.10[t=6.852,P＜0.01],0.81±0.46[t=4.253,P＜0.01] and 2.31±1.27[t=3.030,P＜0.01]).Correlation analysis showed that the ratio of Th17/Treg of the HIV-infected patients was positively correlated with the peripheral CD4+ T cell count (r=0.312 5,P=0.049 6),and negatively correlated with HIV RNA viral load (r=-0.474 7,P=0.002 0).The ratio of Th1/Treg of the HIV-infected patients was positively correlated with the peripheral CD4+ T cell count (r=0.333 5,P=0.035 5).Conclusions Th22,Th17,Th1 and Treg cells in the peripheral blood of HIV-infected patients are closely related to CD4+ T cell count.ART can partially recover immune imbalance,and help to rebuild immune function of HIV-infected patients.

Clinical Significance of IL-22 Expression and Percentage of IL-22-producing Th22 Cells in Primary Sj?gren′s Syndrome / 中国医科大学学报

Objective to measure the percentage of th22 cells and evaluate the levels of plasma interlukin-22(IL-22)in human peripheral blood, so as to determine their clinical significance in primary Sj?gren′s syndrome(pSS). Methods Patients with pSS were divided into three subgroups based on severity of labial gland involvement:mild,moderate and severe. Healthy people served as controls. the percentage of th22 cells and the lev-els of IL-22 in human peripheral blood from pSS patients and healthy controls were measured and compared. Results Compared to healthy con-trols,pSS patients had significantly higher percentage of th22 cells and higher plasma IL-22 levels(P < 0.05). Among pSS patients,the more seri-ous illness they had,the higher percentage of th22 cell and levels of IL-22 were observed. Severe patients had higher percentage of th22 cells and IL-22 levels than moderate patients(P < 0.05),and moderate patients had higher percentage of th22 cells and IL-22 levels than mild patients(P <0.05). Conclusion Increased peripheral IL-22-secreting th22 cells are detected in primary Sj?gren′s syndrome,which have a close association with disease severity. these data suggest that th22 and its released cytokine IL-22 may be considered as potential valuable biomarkers for severity of pSS,which may provide a novel therapeutic target for treatment.

Effect of Baicalin on Th22 and IL-22 in DSS-induced Colitis Mice / 世界科学技术-中医药现代化

This study was aimed to investigate the effect of baicalin on the proportion of Th22 cells and the concentration of IL-22 bothin vivo andin vitro, in order to explore the immune mechanism of baicalin on inflammatory bowel disease mice model. The 3.5% dextran sodium sulfate (DSS) was used on C57BL/6 mice for the establishment of colitis mice model. Mice were randomly divided into the blank control group, model group, and baicalin group. Flow cytometry and ELISA were used in the detection of the proportion of Th22 cells and concentration of IL-22 in peripheral blood serum, respectively. The spleen lymphocytes of mice were isolated and cultured by baicalin medium (0, 10, 20, 40μM) for 48 h. Flow cytometry was used in the detection of the proportion of Th22 cells. The results showed that baicalin reduced the proportion of Th22 cells and the expression of IL-22 bothin vivo andin vitro experiments. It was concluded that baicalin can inhibit Th22 cell differentiation and expression of IL-22in vitro and DSS-induced colitis mice. It indicated that baicalin had a good treatment potential in Th22 cell-mediated inflammatory diseases.

The changes of Th17 and Th22 cells in patients with Helicobacter pylori infection / 国际检验医学杂志

Objective To investigate the changes of Th17 and Th22 cells in patients with Helicobacter pylori(HP)infection . Methods 66 cases of HP infection (HP infection group) and 30 cases of healthy people (control group) were selected .The levels of Th17 and Th22 cells in peripheral blood were measured by flow cytometry and the level of IL-17 and IL-22 in serum were meas-ured by ELISA .Results Comparing with the control group ,the levels of Th17 ,Th22 ,IL-17 and IL-22 were significantly increased in HP infection group(P<0 .05) .The correlation analysis showed that the levels of Th17 ,Th22 ,IL-17 and IL-22 were significantly positive correlated with DPM(P<0 .01) .Conclusion Th17 and Th22 cells were actived in patients with HP infection ,which caused the high expression of immune effector molecules ,and promoted the progress of immune damage .

Relationship and Research Prospects of T Helper Cells and Aplastic Anemia / 浙江中医药大学学报

Objective To review the pathogenesis and research prospects in AA.[Methods] In this paper, we summarize the imbalance mechanism of Th1/Th2, and the relationship of fol icular helper T cells(Tfh),Thl7, Th9 ,Th22 with aplastic anemia. [Results]The imbalance of Th1/Th2 cells leads to bone marrow failure. Immunosuppressive therapy can inhibit Th1 cell, restore the balance. The pathogenesis of Tfh, Thl7, Th9 and Th22 is closely correlated with AA. [Conclusion] AA pathogenesis is complex, CD4+cellsubsets is related to the occurrence and development of AA. Detect the levels of immune cells in the serum of patients is beneficial for diagnosis and treatment of AA.

Change of Th22 cells in peripheral blood of patients with primary biliary cirrhosis and clinical implication / 实用医学杂志

Objective To investigate the change of Th22 cells in the peripheral blood of the patients with primary biliary cirrhosis (PBC) and evaluate its clinical significance. Methods The proportion of Th22 cells in the peripheral blood of PBC patients and healthy controls were evaluated by flow cytometry. The cytokine IL-22 of each group was measured by ELISA and ALT, AST, GGT, TBIL and CRP were measured by Automatic biochemical analyzer. The proportion of Th22 cells correlation with IL-22 , ALT, AST, GGT, TBIL and CRP were analyzed. Results The proportion of Th22 cells was higher in PBC patients than healthy controls (P < 0.05), Moreover the frequency of Th22 was increased in PBC patients with liver cirrhosis than in PBC patients with liver non-cirrhosis (P < 0.05). The level of IL-22, ALT, AST, GGT, TBIL and CRP were increased in PBC patients (P < 0.05). Moreover Th22 frequency of peripheral blood was positively associated with IL-22, ALT, AST, GGT and CRP (P < 0.05). Conclusion Th22 may be involved in the pathogenesis of and it is a potential therapy target for PBC.