T Follicular Helper Cells and Regulatory B Cells Dynamics in Systemic Lupus Erythematosus

Yang, Xue; Yang, Ji; Chu, Yiwei; Yu, Xue; Xuan, Dong; Zheng, Shucong; Zou, Hejian

doi:10.1371/journal.pone.0088441

Cited by 79 publications

(77 citation statements)

References 38 publications

(73 reference statements)

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“…The regulation of T FH frequency, and by extension the regulation of their impact on GC B-cell development and function, is vital to the quality of the humoral immune response (5). While the presence of too few T FH may lead to abortive GC formation and defective B-cell responses, an over-expansion was found to be associated with the prevalence of autoantibodies (6, 7). It is possible that an expansion of T FH also lowers the selection pressure on GC B-cells and leads to the emergence of low-affinity B-cells (8).…”

Section: Introductionmentioning

confidence: 99%

Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian Immunodeficiency Virus–Infected Rhesus Macaques May Contribute to Accumulation of TFH in Chronic Infection

Chowdhury

Rio

Tharp

et al. 2015

The Journal of Immunology

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T follicular helper cells (TFH) are critical for the development and maintenance of germinal centers (GC) and humoral immune responses. During chronic HIV/SIV infection TFH accumulate, possibly as a result of antigen persistence. The HIV/SIV-associated TFH expansion may also reflect lack of regulation by suppressive follicular regulatory CD4+ T-cells (TFR). TFR are natural regulatory T-cells (TREG) that migrate into the follicle and, similarly to TFH, up-regulate CXCR5, Bcl-6, and PD1. Here we identified TFR as CD4+CD25+FoxP3+CXCR5+PD1hiBcl-6+ within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FoxP3, Bcl-6, PRDM1, IL-10, and IL-21. In healthy, SIV-uninfected RM, we observed a negative correlation between frequencies of TFR and both TFH and GC B-cells as well as levels of CD4+ T-cell proliferation. Following SIV infection, the TFR/TFH ratio was reduced with no change in the frequency of TREG or TFR within the total CD4+ T-cell pool. Finally, we examined whether higher levels of direct virus infection of TFR were responsible for their relative depletion post-SIV infection. We found that TFH, TFR and TREG sorted from SIV- infected RM harbor comparable levels of cell-associated viral DNA. Our data suggests that TFR may contribute to the regulation and proliferation of TFH and GC B-cells in vivo and that a decreased TFR/TFH ratio in chronic SIV infection may lead to unchecked expansion of both TFH and GC B-cells.

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Section: Introductionmentioning

confidence: 99%

Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian Immunodeficiency Virus–Infected Rhesus Macaques May Contribute to Accumulation of TFH in Chronic Infection

Chowdhury

Rio

Tharp

et al. 2015

The Journal of Immunology

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“…Once this subset of T cells fails to discriminate self-reactive B cells from the normal antigen-specific B cells, high-affinity autoantibodies would be generated, and thereby autoimmune disease would happen (23). Increasing evidences have shown that TFH cells play an important role in the pathogenesis of autoimmune diseases, such as SLE, RA and IgA nephropathy (17,24,25). Furthermore, researchers revealed that the frequency and higher expression of TFH cells correlate with the disease severity which might involve in the pathogenesis of MG (19,20).…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

et al. 2016

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Results: Higher percentage of thymic TFH cells was found in MG patients with thymoma compared with both thymoma patients without MG and control group. The expression levels of the four markers in thymoma of MG patients were significantly higher than thymoma patients without MG and control group.No significant difference was found in the levels of programmed cell death 1 (PD-1) and Bcl-6 between thymoma patients without MG and the control, while the levels of CXCR5 and ICOS in thymoma patients without MG were higher than control group. Conclusions: These results suggested thymic TFH cells might involve in the pathogenesis of MG with thymoma. However, it needs further study to test if the inhibition of the function of TFH cells could effectively alleviate the severity of MG. 11,12). These cells are characterized by increased expression of numerous molecules including inducible co-stimulator (ICOS), program death 1 (PD-1) and CD40-ligand, the transcription factor B cell lymphoma 6 (Bcl-6) and regulatory cytokines which can promote the development of TFH cells and the interaction of T and B cells (13). Increased numbers of circulating TFH cells and aberrant activation of TFH cells are associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and IgA nephropathy (14-17). Keywords: Myasthenia gravis (MG); thymoma; T follicular helper cells (TFH cells)The numbers of TFH cells in peripheral blood of MG patients are significantly higher than that of healthy control, and the frequency of TFH cells are positively correlated with levels of serum AchR-Ab (18). However, the thymic TFH cells in thymoma patients with MG remain controversial (19,20). In this study, we investigated the percentage of thymic TFH cells around the thymoma region and their activity in thymoma patients with MG. Materials and methods SamplesA total of 50 patients were enrolled who underwent thymectomy at the Department of Thoracic Surgery, Huashan Hospital of FDU between 2013 and 2014. Thirty thymoma patients with MG were recruited as MG group (MG) while another twenty thymoma patients without MG were recruited as non-MG group (NMG). We collected ten control thymic biopsies from cardiac surgery cases of the Department of Cardiovascular Surgery, Huashan Double-labeled immunofluorescence (IF)Endogenous peroxide activity quench were performed with protocols similar to IHC staining. Tissues were incubated with rabbit anti-human CD4 antibody (EPR6855, Abcam) at 37 ℃ for 4 h. Tissues were incubated with mouse antihuman CXC chemokine receptor 5 (CXCR5) monoclonal antibody (Clone51505, Abcam) at 37 ℃ for 24 h. Sections were incubated with Goat anti-Rabbit IgG-heavy and light chain cross-adsorbed antibody dylight ® 488-conjugated affinipure (A90-516D2, Bethyl, USA) at 37 ℃ for 2 h. Sections were incubated with goat anti-mouse IgGheavy and light chain cross-adsorbed antibody dylight ® 594-conjugated affinipure (A120-201D4; Bethyl, USA) at 37 ℃ for 2 h. Finally, the sections were mounted and cov...

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“…Rebampide treatment reduced the number of TFH cells, but increased the number of Breg cells, similar to our results. However, one study reported that TFH cells promoted IL‐10 production during the differentiation of Breg cells in systemic lupus erythematosus . Therefore, the increase in Breg cells may be due to feedback regulation.…”

Section: Discussionmentioning

confidence: 99%

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

Liu

Wang

et al. 2016

Clin Exp Pharma Physio

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The purpose of this study is to elucidate the potential role of interleukin (IL)-10(+) regulatory B cells and other B cell subsets in the development of hepatitis B virus-associated membranous nephropathy (HBV-MN). A total of 14 patients with new onset HBV-MN, 12 individuals with immune-tolerant HBV infection (HBV-IT), and 12 healthy controls (HC) were examined for the percentages of CD38(+) , CD86(+) , CD27(+) , CD95(+) and IL-10(+) B cells by flow cytometry. Serum IL-10 concentration was examined by enzyme-linked immunosorbent assay (ELISA). The percentages of CD38(+) CD19(+) , CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , and CD95(+) CD19(+) B cells were significantly higher in HBV-MN patients than the HBV-IT and HC. The percentages of CD5(+) CD19(+) , IL-10(+) CD19(+) B cells and serum IL-10 level in HBV-MN patients were significantly higher than the HC, and lower than the HBV-IT. Percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells were reduced after treatment, while the percentages of CD5(+) CD1d(+) CD19(+) , CD5(+) CD1d(+) IL-10(+) CD19(+) , and IL-10(+) CD19(+) B cells were increased. The 24 h urinary protein concentration was positively correlated with the percentage of CD38(+) CD19(+) , and negatively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Similarly, the value of eGFR was negatively correlated with the percentage of CD38(+) CD19(+) , and positively correlated with the percentage of IL-10(+) CD19(+) B cells and serum IL-10 level. Serum IL-10 level and the percentage of IL-10(+) CD19(+) were negatively correlated with the percentages of CD38(+) CD19(+) , and CD86(+) CD19(+) B cells. These results suggest that CD86(+) CD19(+) , CD38(+) CD86(+) CD19(+) , CD95(+) CD19(+) , and especially CD38(+) CD19(+) and IL-10(+) CD19(+) cells may participate in the pathogenesis of HBV-MN.

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T Follicular Helper Cells and Regulatory B Cells Dynamics in Systemic Lupus Erythematosus

Cited by 79 publications

References 38 publications

Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian Immunodeficiency Virus–Infected Rhesus Macaques May Contribute to Accumulation of TFH in Chronic Infection

Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian Immunodeficiency Virus–Infected Rhesus Macaques May Contribute to Accumulation of TFH in Chronic Infection

Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

A higher frequency of IL‐10‐producing B cells in Hepatitis B virus‐associated membranous nephropathy

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