Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency
- Author(s)
- Obers, A; Poch, T; Rodrigues, G; Christo, SN; Gandolfo, LC; Fonseca, R; Zaid, A; Kuai, JEY; Lai, H; Zareie, P; Yakou, MH; Dryburgh, L; Burn, TN; Dosser, J; Buquicchio, FA; Lareau, CA; Walsh, C; Judd, L; Theodorou, MR; Gutbrod, K; Dörmann, P; Kingham, J; Stinear, T; Kallies, A; Schroeder, J; Mueller, SN; Park, SL; Speed, TP; Satpathy, AT; Phan, TG; Wilhelm, C; Zaph, C; Evrard, M; Mackay, LK;
- Journal Title
- Immunity
- Publication Type
- Oct 11 epub ahead of print
- Abstract
- 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 β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β 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.
- Keywords
- CD8(+) T cells; Iel; T cell memory; TRM cells; dirty mice; mucosal immunity; retinoic acid; tissue-resident memory T cells; transforming growth factor beta
- Research Division(s)
- Bioinformatics
- PubMed ID
- 39406245
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2024.09.015
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-10-25 10:15:34
Last Modified: 2024-10-25 10:15:53