title: T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis.
abstract: The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-γ and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-γ completely abolished colitis.
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: A A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Weber
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: J R
authors.initials: JR
authors.lastname: Grün
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Löffler
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Haftmann
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Riedel
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Maschmeyer
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Lehmann
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Westendorf
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: M-F
authors.initials: MF
authors.lastname: Mashreghi
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Löhning
authors.affiliation: Universitätsklinikum Regensburg, Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mack
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
authors.forename: H D
authors.initials: HD
authors.lastname: Chang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D020381:Interleukin-17; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma