Browsing by Author "McDonald, Paul W."
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- IL-7 signalling represses Bcl-6 and the TFH gene ProgramMcDonald, Paul W.; Read, Kaitlin A.; Baker, Chandra E.; Anderson, Ashlyn E.; Powell, Michael D.; Ballesteros-Tato, André; Oestreich, Kenneth J. (Nature, 2016-01-08)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-6R∝ 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-6R∝⁺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.