The transcription factor musculin promotes the unidirectional development of peripheral T_reg cells by suppressing the T_H2 transcriptional program.

Although master transcription factors (TFs) are key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress the development of other, non-specific T cell lineages has not been fully elucidated. Through the use of regulatory T cells (T_reg cells) induced by transforming growth factor-β (TGF-β), we identified the TF musculin (MSC) as being critical for the development of induced T_reg cells (iT_reg cells) by repression of the T helper type 2 (T_H2) transcriptional program. Loss of MSC reduced expression of the T_reg cell master TF Foxp3 and induced T_H2 differentiation even under iT_reg-cell-differentiation conditions. MSC interrupted binding of the TF GATA-3 to the locus encoding T_H2-cell-related cytokines and diminished intrachromosomal interactions within that locus. MSC-deficient (Msc^-/-) iT_reg cells were unable to suppress T_H2 responses, and Msc^-/- mice spontaneously developed gut and lung inflammation with age. MSC therefore enforced Foxp3 expression and promoted the unidirectional induction of iT_reg cells by repressing the T_H2 developmental program.

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