Rbpj expression in regulatory T cells is critical for restraining T(H)2 responses

The transcriptional regulator Rbpj is involved in T-helper (T(H)) subset polarization, but its function in T(reg) cells remains unclear. Here we show that T(reg)-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of T(reg) cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient T(reg) cells in controlling T(H)2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a T(H)2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient T(reg) cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived T(H)2-polarized T(reg) cells, with a prevailing signature of the transcription factor Gata-3. Taken together, our study suggests that T(reg) cells require Rbpj to specifically restrain T(H)2 responses, including their own excessive T(H)2-like differentiation potential.