Background Follicular helper T (TFH) cells induce germinal center response to produce high affinity antibodies against a specific pathogen. Excessive formation of TFH cells are closely associated with the onset of antibody-mediated systemic autoimmune diseases, such as systemic lupus erythematosus (SLE). Our previous study has shown that ETV5 promotes murine TFH cell differentiation. However, its role in human TFH cell differentiation and the pathogenesis of SLE has not been investigated.
Methods We analyzed the autoimmune phenotype and cell population in ETV5 deficient lupus mouse models. Autoimmunity was evaluated by checking autoantibody levels, immune cell infiltration into non-lymphoid organs, and kidney IgG deposition. The frequency of TFH, TFR, and GC B cells was measured by flow cytometry. The expression levels of ETV5 in human samples were analyzed by qRT-PCR and western blot.
Results The frequency of TFH cells is decreased in the spleen of T cell-specific ETV5 null mice compared with control mice. In addition, ETV5 deficiency in T cells substantially suppresses autoimmunity in lupus mouse models. TFH cells have higher levels of ETV5 than non-TFH cells in humans as well as in mice. ETV5 overexpression also promotes human TFH cell differentiation. Furthermore, ETV5 levels are significantly higher in CD4 T cells from SLE patients than in those from healthy control, suggesting that ETV5 may be an SLE-promoting factor.
Conclusions In this study, we show that ETV5 is a transcription factor that promotes the pathogenesis of lupus autoimmune disease via enhancing TFH cell differentiation. We are currently investigating the molecular mechanism of how ETV5 promotes TFH cell differentiation.
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