JunB is essential for IL-23-dependent pathogenicity of Th17 cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28555647.
- Also identified by DOI 10.1038/ncomms15628 and PMC identifier 5460000.
- 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
CD4<sup>+</sup> T-helper cells producing interleukin-17 (IL-17), known as T-helper 17 (T<sub>H</sub>17) cells, comprise heterogeneous subsets that exhibit distinct pathogenicity. Although pathogenic and non-pathogenic T<sub>H</sub>17 subsets share a common RORγt-dependent T<sub>H</sub>17 transcriptional programme, transcriptional regulatory mechanisms specific to each of these subsets are mostly unknown. Here we show that the AP-1 transcription factor JunB is critical for T<sub>H</sub>17 pathogenicity. JunB, which is induced by IL-6, is essential for expression of RORγt and IL-23 receptor by facilitating DNA binding of BATF at the Rorc locus in IL-23-dependent pathogenic T<sub>H</sub>17 cells, but not in TGF-β1-dependent non-pathogenic T<sub>H</sub>17 cells. Junb-deficient T cells fail to induce T<sub>H</sub>17-mediated autoimmune encephalomyelitis and colitis. However, JunB deficiency does not affect the abundance of gut-resident non-pathogenic T<sub>H</sub>17 cells. The selective requirement of JunB for IL-23-dependent T<sub>H</sub>17 pathogenicity suggests that the JunB-dependent pathway may be a therapeutic target for autoimmune diseases.
Medical subject headings
- Encephalomyelitis, Autoimmune, Experimental
- Interleukin-17
- Interleukin-23
- Th17 Cells
- Transcription Factors