Autor: |
Paul W. McDonald, Kaitlin A. Read, Chandra E. Baker, Ashlyn E. Anderson, Michael D. Powell, André Ballesteros-Tato, Kenneth J. Oestreich |
Přispěvatelé: |
Virginia Tech |
Jazyk: |
angličtina |
Rok vydání: |
2016 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) |
Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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