| First Author | Manoharan I | Year | 2023 |
| Journal | J Immunol | Volume | 211 |
| Issue | 5 | Pages | 853-861 |
| PubMed ID | 37477694 | Mgi Jnum | J:342474 |
| Mgi Id | MGI:7545434 | Doi | 10.4049/jimmunol.2200909 |
| Citation | Manoharan I, et al. (2023) The Transcription Factor RXRalpha in CD11c+ APCs Regulates Intestinal Immune Homeostasis and Inflammation. J Immunol 211(5):853-861 |
| abstractText | APCs such as dendritic cells and macrophages play a pivotal role in mediating immune tolerance and restoring intestinal immune homeostasis by limiting inflammatory responses against commensal bacteria. However, cell-intrinsic molecular regulators critical for programming intestinal APCs to a regulatory state rather than an inflammatory state are unknown. In this study, we report that the transcription factor retinoid X receptor alpha (RXRalpha) signaling in CD11c+ APCs is essential for suppressing intestinal inflammation by imparting an anti-inflammatory phenotype. Using a mouse model of ulcerative colitis, we demonstrated that targeted deletion of RXRalpha in CD11c+ APCs in mice resulted in the loss of T cell homeostasis with enhanced intestinal inflammation and increased histopathological severity of colonic tissue. This was due to the increased production of proinflammatory cytokines that drive Th1/Th17 responses and decreased expression of immune-regulatory factors that promote regulatory T cell differentiation in the colon. Consistent with these findings, pharmacological activation of the RXRalpha pathway alleviated colitis severity in mice by suppressing the expression of inflammatory cytokines and limiting Th1/Th17 cell differentiation. These findings identify an essential role for RXRalpha in APCs in regulating intestinal immune homeostasis and inflammation. Thus, manipulating the RXRalpha pathway could provide novel opportunities for enhancing regulatory responses and dampening colonic inflammation. |
