| First Author | Shao TY | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 11 | Pages | 113323 |
| PubMed ID | 37889750 | Mgi Jnum | J:342328 |
| Mgi Id | MGI:7548215 | Doi | 10.1016/j.celrep.2023.113323 |
| Citation | Shao TY, et al. (2023) Kruppel-like factor 2+ CD4 T cells avert microbiota-induced intestinal inflammation. Cell Rep 42(11):113323 |
| abstractText | Intestinal colonization by antigenically foreign microbes necessitates expanded peripheral immune tolerance. Here we show commensal microbiota prime expansion of CD4 T cells unified by the Kruppel-like factor 2 (KLF2) transcriptional regulator and an essential role for KLF2+ CD4 cells in averting microbiota-driven intestinal inflammation. CD4 cells with commensal specificity in secondary lymphoid organs and intestinal tissues are enriched for KLF2 expression, and distinct from FOXP3+ regulatory T cells or other differentiation lineages. Mice with conditional KLF2 deficiency in T cells develop spontaneous rectal prolapse and intestinal inflammation, phenotypes overturned by eliminating microbiota or reconstituting with donor KLF2+ cells. Activated KLF2+ cells selectively produce IL-10, and eliminating IL-10 overrides their suppressive function in vitro and protection against intestinal inflammation in vivo. Together with reduced KLF2+ CD4 cell accumulation in Crohn's disease, a necessity for the KLF2+ subpopulation of T regulatory type 1 (Tr1) cells in sustaining commensal tolerance is demonstrated. |
