Résumé
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-beta (TGF-(3), we identified the TF musculin (MSC) as being critical for the development of induced Treg cells (iT(reg) cells) by repression of the T helper type 2 (T(H)2) transcriptional program. Loss of MSC reduced expression of the Treg cell master TF Foxp3 and induced TH2 differentiation even under iT(reg)-cell-differentiation conditions. MSC interrupted binding of the TF GATA-3 to the locus encoding T(H)2-cell-related cytokines and diminished intrachromosomal interactions within that locus. MSC-deficient (Msc(-/-)) iTreg cells were unable to suppress T(H)2 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(H)2 developmental program.