Abstract
Abstract The expression of the transcriptional repressor Bcl-6 has been commonly linked to the development of both the CD4+ T follicular helper (TFH) and T central memory (TCM) cell types. Here, we demonstrate that in response to decreased interleukin 2 (IL-2) signaling, Bcl-6 expression is increased in effector T helper 1 (TH1) cells. Consequently, this results in the promotion of both TFH and TCM-like gene programs including expression of Il6ra and Il7r. Strikingly, exposure of this potentially bi-potent cell population to interleukin 7 (IL-7) results in a significant decrease in TFH-associated gene expression patterns including that of Bcl6 and Cxcr5, but not in TCM-specific genes including Sell and Klf2. The decrease in the TFH-profile is dependent upon a repressive complex that includes the IL-7 responsive transcription factor Stat5. These data support a model by which IL-7 signaling specifies TCM cell fate by repressing the TFH gene program.
Published Version
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