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Regulatory T cells (Tregs) are very important for maintaining immune homeostasis and prevent autoimmune diseases. The Foxp3-expressing CD4+ regulatory cells need to differentiate into effector Treg (eTreg) cells to maintain the immune homeostasis. The transcription factor, IRF4 has been reported to be essential for the eTreg differentiation upon TCR-stimulation, but how IRF4 activity is regulated is not very clear. Herein, we show that the AP-1 transcription factor, JunB, is expressed in etreg cells and promotes an IRF4-dependent transcription program. Mice lacking JunB in Treg cells develop multi-organ autoimmunity. JunB promotes expression of Treg effector molecules, such as ICOS and CTLA4, and also is important for homeostasis and suppressive functions of eTreg. JunB, facilitates the accumulation of IRF4 at a subset of IRF4 target sites, including those located near Icos and Ctla4. Therefore, we show JunB as a critical regulator of IRF4-dependent Treg effector programs, highlighting importance of AP-1 factors in Treg-mediated immune homeostasis. |