title: Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis.
abstract: Th17 cells reactive to the enteric microbiota are central to the pathogenesis of certain types of inflammatory bowel disease. However, Th17 cells display substantial developmental plasticity, such that some progeny of Th17 cell precursors retain a predominantly IL-17A(+) phenotype, whereas others extinguish IL-17 expression and acquire expression of IFN-γ, giving rise to "Th1-like" cells. It remains unclear what role these subsets play in inflammatory bowel disease. Using a Th17 transfer model of colitis, we found that IFN-γ-deficient Th17 cells retained an IL-17A(+) phenotype and were unable to induce colitis in recipients. Development of disease required the transition of a subset of Th17 precursors to Th1-like cells and was contingent on the expression of both Stat4 and T-bet, but not the IL-12 or IFN-γ receptors. Moreover, Th17 cells could provide "help" for the development of pathogenic Th1 cells from naïve precursors. These results indicate that Th17 cells are potent mediators of colitis pathogenesis by dual mechanisms: by directly transitioning to Th1-like cells and by supporting the development of classic Th1 cells.
authors.affiliation: Department of Pathology.
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Harbour
authors.affiliation: Department of Pathology.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Maynard
authors.affiliation: Department of Pathology.
authors.forename: Carlene L
authors.initials: CL
authors.lastname: Zindl
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.affiliation: Department of Pathology cweaver@uab.edu.
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000503:physiopathology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050797:STAT4 Transcription Factor / Q000378:metabolism; D018709:Statistics, Nonparametric; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
keywords: Th1; Th17; colitis