IL-7 signalling represses Bcl-6 and the T FH gene program

Academic Article


  • The transcriptional repressor Bcl-6 is linked to the development of both CD4 + T follicular helper (T FH) and central memory T (T CM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (T H 1) cells upregulate Bcl-6 and co-initiate T FH - and T CM -like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the T FH gene program, whereas IL-7 signalling represses T FH -associated genes including Bcl6 and Cxcr5, but not the T CM -related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Rα + 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 T FH gene program and evoke a divergent regulatory mechanism by which post-effector T H 1 cells may contribute to long-term cell-mediated and humoral immunity.
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    Author List

  • McDonald PW; Read KA; Baker CE; Anderson AE; Powell MD; Ballesteros-Tato A; Oestreich KJ
  • Volume

  • 7