Rbpj expression in regulatory T cells is critical for restraining TH2 responses

• Published in: Nature communications 2019-04, Vol.10 (1), p.1621-20, Article 1621
• Main Authors: Delacher, Michael, Schmidl, Christian, Herzig, Yonatan, Breloer, Minka, Hartmann, Wiebke, Brunk, Fabian, Kägebein, Danny, Träger, Ulrike, Hofer, Ann-Cathrin, Bittner, Sebastian, Weichenhan, Dieter, Imbusch, Charles D., Hotz-Wagenblatt, Agnes, Hielscher, Thomas, Breiling, Achim, Federico, Giuseppina, Gröne, Hermann-Josef, Schmid, Roland M., Rehli, Michael, Abramson, Jakub, Feuerer, Markus
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/31; 38/23; 38/39; 45/61; 631/250/1619; 631/250/1619/554; 631/250/1619/554/1898/1271; 64/60; Chromatin; Class switching; Clonal deletion; GATA-3 protein; Gene expression; Germinal centers; Humanities and Social Sciences; Immunoregulation; Lymphadenopathy; Lymphocytes; Lymphocytes B; Lymphocytes T; multidisciplinary; Nematodes; Phenotypes; Polarization; Science; Science (multidisciplinary); Splenomegaly; T cell receptors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09276-w

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. Transcriptional regulator Rbpj is involved in T-helper subset differentiation. Here the authors show that expression of Rbpj in regulatory T cells is required to both regulate T H 2 responses and regulate T reg T H 2 differentiation potential.