TY  - JOUR
AU  - Delacher, Michael
AU  - Schmidl, Christian
AU  - Herzig, Yonatan
AU  - Breloer, Minka
AU  - Hartmann, Wiebke
AU  - Brunk, Fabian
AU  - Kägebein, Danny
AU  - Träger, Ulrike
AU  - Hofer, Ann-Cathrin
AU  - Bittner, Sebastian
AU  - Weichenhan, Dieter
AU  - Imbusch, Charles D
AU  - Hotz-Wagenblatt, Agnes
AU  - Hielscher, Thomas
AU  - Breiling, Achim
AU  - Federico, Giuseppina
AU  - Gröne, Hermann-Josef
AU  - Schmid, Roland M
AU  - Rehli, Michael
AU  - Abramson, Jakub
AU  - Feuerer, Markus
TI  - Rbpj expression in regulatory T cells is critical for restraining TH2 responses.
JO  - Nature Communications
VL  - 10
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2019-01092
SP  - 1621
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30962454
C2  - pmc:PMC6453958
DO  - DOI:10.1038/s41467-019-09276-w
UR  - https://inrepo02.dkfz.de/record/143508
ER  -