BioProject

The differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells is strictly controlled by T cell receptor (TCR) signals; however, the molecular regulators of these processes are incompletely known. More...

The differentiation and homeostasis of Foxp3+ regulatory T (Treg) cells is strictly controlled by T cell receptor (TCR) signals; however, the molecular regulators of these processes are incompletely known. Here we found that Bach2 was a key regulator of Treg cell differentiation and homeostasis downstream of TCR signalling. Bach2 prevented premature differentiation of fully suppressive effector (e)Treg cells, limited IL-10 production and was required for the development of peripherally induced (p)Treg cells in the gastrointestinal tract. We found that Bach2 attenuated TCR signalling-induced and IRF4-dependent Treg cell differentiation programs. Deletion of IRF4 promoted inducible Treg cell differentiation and rescued pTreg cell differentiation in the absence of Bach2. In turn, loss of Bach2 normalised eTreg cell differentiation of IRF4-deficient Treg cells. Mechanistically, Bach2 counteracted DNA-binding activity of IRF4 and limited chromatin accessibility, thereby attenuating IRF4-dependent transcriptional programs. Thus, Bach2 balanced TCR signalling induced transcriptional activity of IRF4 to maintain Treg cell homeostasis. Overall design: Transcriptional profiling of flow cytometrically sorted naïve CD4+ T cells from wildtype, Bach2-deficient, IRF4-deficient and Bach2/IRF4 double deficient mice, cultured in Treg cell inducing conditions for 0, 24 or 72 hours. Less...