| Autor: |
Chang, Yinshui, Bach, Luisa, Hasiuk, Marko, Wen, Lifen, Elmzzahi, Tarek, Tsui, Carlson, Gutiérrez-Melo, Nicolás, Steffen, Teresa, Utzschneider, Daniel T., Raj, Timsse, Jost, Paul Jonas, Heink, Sylvia, Cheng, Jingyuan, Burton, Oliver T., Zeiträg, Julia, Alterauge, Dominik, Dahlström, Frank, Becker, Jennifer-Christin, Kastl, Melanie, Symeonidis, Konstantinos |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 93, p1-19, 19p |
| Abstrakt: |
T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor–β (TGF-β) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-β–induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo–generated TFH cells and provide critical help to B cells. The study further reveals that TGF-β–induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-β–containing T helper 17 (TH17)–inducing conditions also yield separate CXCR5+ and IL-17A–producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-β–induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-β–rich environments in vitro and in vivo. Editor's summary: Effective antibody responses require T follicular helper cells (TFH) to provide help to B cells. Our understanding of T cell biology has been greatly facilitated by in vitro studies; however, a robust method to differentiate murine TFH cells in vitro is lacking. Chang et al. found that supplementing murine CD4+ T cells cultured under TFH and TH17-polarizing conditions with TGF-β promoted differentiation of TFH-like cells, which phenotypically and functionally resembled in vivo–generated TFH cells. The transcription factor c-Maf was required to drive the fate of naïve CD4+ T cells toward TFH rather than TH17 cells. This work demonstrates that TGF-β–mediated differentiation of murine TFH cells is determined by c-Maf. —Hannah Isles [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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