Rbpj expression in regulatory T cells is critical for restraining TH2 responses [spleen RbpjKO and RbpjWT RNA-seq]

The transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing footprint of the transcription factor Gata-3. Taken together, our study suggest that Treg cells require Rbpj to specifically restrain TH2 responses, including their own excessive TH2-like differentiation potential. Overall design: We isolated Treg cells from spleens of affected Treg Rbpj-deficient animals and wildtype counterparts. Total RNA was isolated and subjected to gene expression analysis using RNA sequencing

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Delacher M, Schmidl C, Herzig Y, Breloer M, Hartmann W, Brunk F, Kägebein D, Träger U, Hofer AC, Bittner S, Weichenhan D, Imbusch CD, Hotz-Wagenblatt A, Hielscher T, Breiling A, Federico G, Gröne HJ, Schmid RM, Rehli M, Abramson J, Feuerer M