| First Author | Schwartz DM | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 1 | Pages | 106-120.e10 |
| PubMed ID | 30650370 | Mgi Jnum | J:360952 |
| Mgi Id | MGI:6381189 | Doi | 10.1016/j.immuni.2018.12.014 |
| Citation | Schwartz DM, et al. (2019) Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology. Immunity 50(1):106-120.e10 |
| abstractText | CD4(+) T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARalpha to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during Th differentiation to multiple subsets. RA effects were subset-selective and were most significant in Th9 cells. RA globally antagonized Th9-promoting transcription factors and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARalpha. RA-RARalpha activity limited murine Th9-associated pulmonary inflammation, and human allergic inflammation was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARalpha signaling in Th differentiation, arguing for a role for RA in interleukin 9 (IL-9) related diseases. |
