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.

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 .

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.

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.

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.

Frequency of T helper type 22 cells and expression of interleukin-22 in peripheral blood of patients with psoriasis vulgaris / 中华皮肤科杂志

Objective To determine the frequency of T helper type 22 (Th22) cells and expression level of interleukin-22 (IL-22) in peripheral blood of patients with psoriasis vulgaris,and to investigate their relationship with disease severity and clinical course.Methods Peripheral blood samples were obtained from 40 patients with psoriasis vulgaris and 30 healthy human controls.Five-color flow cytometry was performed to determine the percentage of Th22 cells in peripheral blood,and enzyme-linked immunosorbent assay (ELISA) to measure the expression of serum IL-22.Statistical analysis was carried out by t test and Pearson correlation analysis.Results Both the percentage of Th22 cells and serum level of IL-22 in peripheral blood were significantly higher in patients with psoriasis vulgaris than in healthy human controls (Th22 cells:0.65％ ± 0.48％ vs.0.33％ ± 0.15％,t =3.89,P ＜ 0.01; IL-22:(67.96 ± 14.32) vs.(40.59 ± 9.91) ng/L,t =9.45,P ＜ 0.01).Further more,Th22 cell percentage and IL-22 serum level in peripheral blood were both positively correlated with psoriasis area and severity index (PASI) in these patients (r =0.38,0.94,P ＜ 0.05 and 0.01,respectively),but neither of them correlated with clinical course of psoriasis vulgaris (r =0.20,0.10,respectively,both P ＞ 0.05).Conclusions The percentage of Th22 cells and level of IL-22 are increased in peripheral blood of patients with psoriasis vulgaris,and both of them are correlated with disease severity.

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.