| First Author | Chang Y | Year | 2024 |
| Journal | Sci Immunol | Volume | 9 |
| Issue | 93 | Pages | eadd4818 |
| PubMed ID | 38427718 | Mgi Jnum | J:354960 |
| Mgi Id | MGI:7736808 | Doi | 10.1126/sciimmunol.add4818 |
| Citation | Chang Y, et al. (2024) TGF-beta specifies T(FH) versus T(H)17 cell fates in murine CD4(+) T cells through c-Maf. Sci Immunol 9(93):eadd4818 |
| abstractText | T follicular helper (T(FH)) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T(FH) cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-beta (TGF-beta) induces robust expression of T(FH) hallmark molecules CXCR5 and Bcl6 in activated mouse CD4(+) T cells in vitro. TGF-beta-induced mouse CXCR5(+) T(FH) cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T(FH) cells and provide critical help to B cells. The study further reveals that TGF-beta-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-beta-containing T helper 17 (T(H)17)-inducing conditions also yield separate CXCR5(+) and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of T(FH) and T(H)17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-beta-induced T(FH) cell program, that T(FH) and T(H)17 cells share a common developmental stage, and that c-Maf acts as a switch factor for T(FH) versus T(H)17 cell fates in TGF-beta-rich environments in vitro and in vivo. |
