Rbpj expression in regulatory T cells is critical for restraining T<sub>H</sub>2 responses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30962454.
- Also identified by DOI 10.1038/s41467-019-09276-w and PMC identifier 6453958.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The transcriptional regulator Rbpj is involved in T-helper (T<sub>H</sub>) subset polarization, but its function in T<sub>reg</sub> cells remains unclear. Here we show that T<sub>reg</sub>-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of T<sub>reg</sub> cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient T<sub>reg</sub> cells in controlling T<sub>H</sub>2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a T<sub>H</sub>2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient T<sub>reg</sub> cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived T<sub>H</sub>2-polarized T<sub>reg</sub> cells, with a prevailing signature of the transcription factor Gata-3. Taken together, our study suggests that T<sub>reg</sub> cells require Rbpj to specifically restrain T<sub>H</sub>2 responses, including their own excessive T<sub>H</sub>2-like differentiation potential.
Medical subject headings
- Immunity, Cellular
- Immunoglobulin J Recombination Signal Sequence-Binding Protein
- Strongyloidiasis
- T-Lymphocytes, Regulatory
- Th2 Cells