Delacher, Michael and Schmidl, Christian and Herzig, Yonatan and Breloer, Minka and Hartmann, Wiebke and Brunk, Fabian and Kaegebein, Danny and Traeger, Ulrike and Hofer, Ann-Cathrin and Bittner, Sebastian and Weichenhan, Dieter and Imbusch, Charles D. and Hotz-Wagenblatt, Agnes and Hielscher, Thomas and Breiling, Achim and Federico, Giuseppina and Groene, Hermann-Josef and Schmid, Roland M. and Rehli, Michael and Abramson, Jakub and Feuerer, Markus (2019) Rbpj expression in regulatory T cells is critical for restraining T(H)2 responses. NATURE COMMUNICATIONS, 10: 1621. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA-METHYLATION; GATA3 EXPRESSION; NOTCH; PROTEIN; HOMEOSTASIS; ACTIVATION; SPECIALIZATION; INFLAMMATION; TOLERANCE; INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2020 07:06 |
| Last Modified: | 14 Apr 2020 07:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27183 |
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