| First Author | McDonald PW | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10285 | PubMed ID | 26743592 |
| Mgi Jnum | J:235894 | Mgi Id | MGI:5803919 |
| Doi | 10.1038/ncomms10285 | Citation | McDonald PW, et al. (2016) IL-7 signalling represses Bcl-6 and the TFH gene program. Nat Commun 7:10285 |
| abstractText | The transcriptional repressor Bcl-6 is linked to the development of both CD4(+) T follicular helper (TFH) and central memory T (TCM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (TH1) cells upregulate Bcl-6 and co-initiate TFH- and TCM-like gene programs, including expression of the cytokine receptors IL-6Ralpha and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the TFH gene program, whereas IL-7 signalling represses TFH-associated genes including Bcl6 and Cxcr5, but not the TCM-related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Ralpha(+)IL-7R(+) CD4(+) T cells emerge from the effector population at late time points post influenza infection. These data support a novel role for IL-7 in the repression of the TFH gene program and evoke a divergent regulatory mechanism by which post-effector TH1 cells may contribute to long-term cell-mediated and humoral immunity. |
