| First Author | Obers A | Year | 2024 |
| Journal | Immunity | Volume | 57 |
| Issue | 11 | Pages | 2615-2633.e10 |
| PubMed ID | 39406245 | Mgi Jnum | J:358145 |
| Mgi Id | MGI:7779479 | Doi | 10.1016/j.immuni.2024.09.015 |
| Citation | Obers A, et al. (2024) Retinoic acid and TGF-beta orchestrate organ-specific programs of tissue residency. Immunity 57(11):2615-2633.e10 |
| abstractText | Tissue-resident memory T (T(RM)) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T(RM) cell fate remains poorly understood. Here, we show that whereas skin T(RM) cells strictly require transforming growth factor beta (TGF-beta) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-beta-independent tissue residency program in the liver and synergizing with TGF-beta to drive T(RM) cells in the small intestine. We found that RA was required for the long-term maintenance of intestinal T(RM) populations, in part by impeding their retrograde migration. Moreover, enhanced RA signaling modulated T(RM) cell phenotype and function, a phenomenon mirrored in mice with increased microbial diversity. Together, our findings reveal RA as a fundamental component of the host-environment interaction that directs immunosurveillance in tissues. |
