Kruppel-like factor 2+ CD4 T cells avert microbiota-induced intestinal inflammation. Cell Rep 2023 Nov 28;42(11):113323
Date
10/27/2023Pubmed ID
37889750Pubmed Central ID
PMC10822050DOI
10.1016/j.celrep.2023.113323Scopus ID
2-s2.0-85174807435 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Shao TY, Jiang TT, Stevens J, Russi AE, Troutman TD, Bernieh A, Pham G, Erickson JJ, Eshleman EM, Alenghat T, Jameson SC, Hogquist KA, Weaver CT, Haslam DB, Deshmukh H, Way SSAuthor
Emily M. Eshleman PhD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
Inflammation
Interleukin-10
Kruppel-Like Transcription Factors
Mice
Microbiota
T-Lymphocytes, Regulatory
Transcription Factors
