| First Author | Zhou JY | Year | 2023 |
| Journal | Immunohorizons | Volume | 7 |
| Issue | 6 | Pages | 456-466 |
| PubMed ID | 37314833 | Mgi Jnum | J:354072 |
| Mgi Id | MGI:7719117 | Doi | 10.4049/immunohorizons.2200071 |
| Citation | Zhou JY, et al. (2023) Intestinal Tr1 Cells Confer Protection against Colitis in the Absence of Foxp3+ Regulatory T Cell-Derived IL-10. Immunohorizons 7(6):456-466 |
| abstractText | The intestinal mucosa is continually exposed to diverse microbial and dietary Ags, requiring coordinated efforts by specialized populations of regulatory T cells (Tregs) to maintain homeostasis. Suppressive mechanisms used by intestinal Tregs include the secretion of anti-inflammatory cytokines such as IL-10 and TGF-beta. Defects in IL-10 signaling are associated with severe infantile enterocolitis in humans, and mice deficient in IL-10 or its receptors develop spontaneous colitis. To determine the requirement of Foxp3+ Treg-specific IL-10 for protection against colitis, we generated Foxp3-specific IL-10 knockout (KO) mice (IL-10 conditional KO [cKO] mice). Colonic Foxp3+ Tregs isolated from IL-10cKO mice showed impaired ex vivo suppressive function, although IL-10cKO mice maintained normal body weights and developed only mild inflammation over 30 wk of age (in contrast to severe colitis in global IL-10KO mice). Protection from colitis in IL-10cKO mice was associated with an expanded population of IL-10-producing type 1 Tregs (Tr1, CD4+Foxp3-) in the colonic lamina propria that produced more IL-10 on a per-cell basis compared with wild-type intestinal Tr1 cells. Collectively, our findings reveal a role for Tr1 cells in the gut, as they expand to fill a tolerogenic niche in conditions of suboptimal Foxp3+ Treg-mediated suppression and provide functional protection against experimental colitis. |
