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

Michael Delacher, Christian Schmidl, Yonatan Herzig, Minka Breloer, Wiebke Hartmann, Fabian Brunk, Danny Kägebein, Ulrike Träger, Ann-Cathrin Hofer, Sebastian Bittner, Dieter Weichenhan, Charles D. Imbusch, Agnes Hotz-Wagenblatt, Thomas Hielscher, Achim Breiling, Giuseppina Federico, Hermann-Josef Gröne, Roland M. Schmid, Michael Rehli, Jakub Abramson and Markus Feuerer ()
Additional contact information
Michael Delacher: University Regensburg and University Hospital Regensburg
Christian Schmidl: University Regensburg and University Hospital Regensburg
Yonatan Herzig: Weizmann Institute of Science
Minka Breloer: Bernhard Nocht Institute for Tropical Medicine
Wiebke Hartmann: Bernhard Nocht Institute for Tropical Medicine
Fabian Brunk: German Cancer Research Center (DKFZ)
Danny Kägebein: German Cancer Research Center (DKFZ)
Ulrike Träger: German Cancer Research Center (DKFZ)
Ann-Cathrin Hofer: German Cancer Research Center (DKFZ)
Sebastian Bittner: University Regensburg and University Hospital Regensburg
Dieter Weichenhan: German Cancer Research Center (DKFZ)
Charles D. Imbusch: German Cancer Research Center (DKFZ)
Agnes Hotz-Wagenblatt: German Cancer Research Center (DKFZ)
Thomas Hielscher: German Cancer Research Center (DKFZ)
Achim Breiling: German Cancer Research Center (DKFZ)
Giuseppina Federico: German Cancer Research Center (DKFZ)
Hermann-Josef Gröne: German Cancer Research Center (DKFZ)
Roland M. Schmid: Technical University of Munich
Michael Rehli: University Regensburg and University Hospital Regensburg
Jakub Abramson: Weizmann Institute of Science
Markus Feuerer: University Regensburg and University Hospital Regensburg

Nature Communications, 2019, vol. 10, issue 1, 1-20

Abstract: Abstract 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 signature of the transcription factor Gata-3. Taken together, our study suggests that Treg cells require Rbpj to specifically restrain TH2 responses, including their own excessive TH2-like differentiation potential.

Date: 2019
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DOI: 10.1038/s41467-019-09276-w

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