The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells
The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells
Haikun Wang, Jianlin Geng, Xiaomin Wen, Enguang Bi, Andrew V Kossenkov, Amaya I Wolf, Jeroen Tas, Youn Soo Choi, Hiroshi Takata, Timothy J Day, Li-Yuan Chang, Stephanie L Sprout, Emily K Becker, Jessica Willen, Lifeng Tian, Xinxin Wang, Changchun Xiao, Ping Jiang, Shane Crotty, Gabriel D Victora, Louise C Showe, Haley O Tucker, Jan Erikson & Hui Hu.
Nat. Immunol., (2014) 15, 667-675
Speaker: Yu Cheng (程玉) Time: 13:00-14:00, Dec 3, 2014
Commentator: Dr. Yee-Shin Lin (林以行老師) Place: Room 601
Abstract:
Follicular helper T cells (TFH ) are essential for B cell formation of germinal centers and long-lived high affinity antibody production, while excess activity may lead to autoimmune response. Previous studies showed that TFH cells are characterized by the expression of molecules that facilitate functional interactions with B cells, including the chemokine receptor CXCR5, the cytokine interleukin 21 (IL-21) and the co-stimulatory molecules programmed death-1 (PD-1) and ICOS. In TFH development, it was reported that Bcl-6 and its antagonist Blimp-1 are key regulators, and several other transcription factors (IRF4, MAF and BATF) are also important. Despite these findings, the molecular mechanism of TFH differentiation is still elusive. The transcription factor Foxp1 of forkhead box (‘Fox’) family, which has four alternative splice isoforms (Foxp1A- Foxp1D), is important to the maintenance and generation of naïve T cells quiescence. In this study, the authors generated Foxp1-deficient CD4+ T cells, which lead to preferentially differentiate to TFH cells with enhancing GC response and increasing antigen-specific isotype-switched antibodies. The authors found that Foxp1 suppresses TFH differentiation through the mechanism of inhibitions the expression of IL-21 directly and ICOS indirectly. Depending on these finding, the authors suggest that Foxp1 may serve as a rate-limiting ‘double-check’ negative regulator in TFH differentiation through the expression of constitutive Foxp1A and TCR-induced Foxp1D.
References:
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