The role of Th22 cells, from tissue repair to cancer progression.

CD4+ T helper (Th) cells play a significant role in modulating host defense. In the presence of lineage specific cytokine cocktail, Naive CD4+ T cells can differentiate into several categories with distinct cytokines profile and effector functions. Th22 cells are a recently identified subset of CD4+ T cell, which differentiate from Naive CD4+ T in the presence of IL-6 and TNF-α. Th22 characterized by the production of interleukin-22 (IL-22) and expression of aryl hydrocarbon receptor (AHR). The main function of Th22 cells is to participate in mucosal defense, tissue repair, and wound healing. However, controversial data have shown that overexpression of IL-22 can lead to pathological changes under inflammatory conditions and tumor progression. This review summarizes our knowledge about the role of Th22 and IL-22 cells in tumor progression through induction of inflammation.

Analysis of Th22, Th17 and CD4+cells co-producing IL-17/IL-22 at different stages of human colon cancer.

T-helper (Th) 22 cells are involved in the immunopathogenesis of inflammatory diseases, but their specific role in the immunopathogenesis of cancer is unknown. In this study, we examined the profile of circulating and intratumoral Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 in colon cancer (CC) patients in relation to tumor staging. Thirty newly diagnosed colon cancer (CC) patients participated in this study. The percentage of Th1 (CD4+IFN-γ+IL-17-IL-22-), Th17 (CD4+IFN-γ-IL-17+IL-22-), Th22 (CD4+IFN-γ-IL-17-IL-22+) and CD4+ cells co-producing IL-17/IL-22 (CD4+IFN-γ-IL-17+IL-22+) in the peripheral blood, tumor and paratumor tissues was assessed by multicolor flow cytometry. The percentage of circulating Th17 and Th22 cells was significantly increased in CC patients compared to that in healthy controls (HCs). In addition, the percentage of infiltrating Th1, Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 was significantly increased in the tumor tissues compared to that in the parartumor tissues. Furthermore, we also found that the percentage of circulating and intratumoral Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 was higher in advanced stages than in early stages. Our findings revealed that Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 were accumulated in colon cancer tissues and may be involved in the tumor development and progression. A better comprehension of the immunopathogenesis of Th17, Th22 and CD4+ cells co-producing IL-17/IL-22 in colon cancer patients would help in the development of novel therapies.

Tolerogenic probiotics: potential immunoregulators in Systemic Lupus Erythematosus.

Probiotics are commensal or nonpathogenic microbes that colonize the gastrointestinal tract and confer beneficial effects on the host through several mechanisms such as competitive exclusion, anti-bacterial effects, and modulation of immune responses. There is growing evidence supporting the immunomodulatory ability of some probiotics. Several experimental and clinical studies have been shown beneficial effect of some probiotic bacteria, particularly Lactobacillus and Bifidobacteria strains, on inflammatory and autoimmune diseases. Systemic lupus erythematosus (SLE) is an autoimmune disease that is mainly characterized by immune intolerance towards self-antigens. Some immunomodulatory probiotics have been found to regulate immune responses via tolerogenic mechanisms. Dendritic and T regulatory (Treg) cells, IL-6, IFN-γ, IL-17, and IL-23 can be considered as the most determinant dysregulated mediators in tolerogenic status. As demonstrated by documented experimental and clinical trials on inflammatory and autoimmune diseases, a number of probiotic bacterial strains can restore tolerance in host through modification of such dysregulated mediators. Since there are limited reports regarding to impact of probiotic supplementation in SLE patients, the preset review was aimed to suggest a number of probiotics bacteria, mainly from Bifidobacteria and Lactobacillus strains that are able to ameliorate immune responses. The aim was followed through literature survey on immunoregulatory probiotics that can restore tolerance and also modulate the important dysregulated pro/anti-inflammatory cytokines contributing to the pathogenesis of SLE.

CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in gastric cancer patients.

BACKGROUND: CD4+(TH1, and TH2) cell groups in the point of view of chemokine receptor expression were considered in blood of stomach cancer patients. MATERIALS AND METHODS: The percentage of blood CD4+ T cells expressing chemokine receptors (before and after gastrectomy) was determined by flow cytometry (Becton Dickinson, USA) using the following chemokine receptor antibodies: anti-CCR5, anti-CXCR3, anti-CCR3 and anti-CCR4. RESULTS: The means of CD4(+) CCR5(+) expressing cells was 1.23% ± 0.90, 0.83% ± 0.34 and 1.34% ± 0.74 in control, pre- and post-operation groups, respectively. CD4(+) CXCR3(+) expressing cells were 19.09% ± 8.4, 16.95% ± 5.71 and 25.08% ± 9.31, respectively. Similar pattern was seen for CD4(+) CCR3(+) and CD4(+) CCR4(+) expressing cells. Pearson correlation analysis shows no relationship between CCR3 and CCR4 expressions on TCD4 cells (r = 0.211, P = 0.126). The complex expression TH1 (CD4(+) CXCR3(+) CCR5(+)) receptors determined 1.14% ± 0.54 for control group, 0.86% ± 0.49 for pre-T and 1.57% ± 0.67 for post-T group. Moreover, the TH2 (CD4(+) CCR3(+) CCR4(+)) expression was 1.60% ± 1.05 for control group, 1.57% ± 0.83 for pre-T and 1.27% ± 0.66 for post-treatment group. Pearson correlation analysis shows that only the CCR3 and CCR5 expression was statistically correlated (r = 0.321, P = 0.018). CONCLUSION: Due to low expression of CCR5 in TH1 and CCR3 in TH2 cells, it seems that utility of these is extremely limited for clinical evaluation, but not scientific purpose. Moreover, considering the CXCR3 for TH1 cells and CCR4 expression for TH2 cells, due to considerable expression, may be practical.

Expression of chemokine receptors on Th1/Th2 CD4+ lymphocytes in patients with multiple sclerosis.

BACKGROUND: Th1 cells preferentially express CXCR3, CCR5 and CCR6, while CCR3 and CCR4 are predominantly expressed by Th2 cell subsets. Multiple Sclerosis (MS) is a Th1 cell-dependant chronic inflammatory disease of the central nervous system, and immunomudolatory cytokines could alter the chemokine expression pattern of these lymphocyte subsets. OBJECTIVE: This study was performed to measure chemokine receptor expression on CD4 T cells for evaluation of Th1/Th2 dominantly in IFN-ß treated patients. METHODS: Flowcytometry was used to detect chemokine receptor expression on CD4 T cell population in PBMCs obtained from MS and healthy control groups. Twenty six MS patients participated in this study before and after IFN-ß therapy and the same number of healthy individuals were included. RESULTS: The percentage of lymphocytes was 41.28% ± 10.30% 2 in the blood of MS group compared with 36.88% ± 5.51% in the control group (p=0.017). The CD4+CXCR3+ cells were 18.86% ± 8.46% in healthy group, 30.78% ± 9.8% in pre-treated MS patients and 21.06% ± 9.23% in post-treated group (p<0.001). The CD4+CCR4+ cell subsets were 27.35% ± 10.15% in healthy group; 28.17% ± 8.9% in pre-treated group and 34.20% ± 8.96% in the post-IFN-ß treatment group. The subset of CD4+CCR4+ was found to be dominant after IFN-ß therapy in comparison with the control group (p<0.001). CD4+CCR5+ percentage was 1.24% ± 0.92% in the healthy people, 1.23% ± 0.71% in the MS patients and 0.76% ± 0.49% in post-treatment status (p=0.003). CD4+CCR3+ cell subsets were 0.62% ± 0.67% in control group, 0.28% ± 0.26% in the MS patients (p=0.022) and 0.39% ± 0.54% in IFN-ß treated patients (p=0.334). An association was found for CXCR3 expression in pre- and post-treatment status (r=0.840, p<0.001) as well as for CCR4+ expression (r=0.712, p<0.001) in the same groups. The Th1 response was dominant in pre-treatment states, and then it shifted to a Th2 dominant state after IFN-ß treatment. CONCLUSION: We suggest that the chemokine receptor expression of Th1/Th2 cell subsets could be used for monitoring and the evaluation of the MS disease status.