title: IL-18Rα-deficient CD4(+) T cells induce intestinal inflammation in the CD45RB(hi) transfer model of colitis despite impaired innate responsiveness.
abstract: IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4(+) T-cell function remains unclear. Here we show that murine intestinal CD4(+) T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RB(hi) T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ(+) , IL-17(+) , and IL-17(+) IFN-γ(+) effector CD4(+) T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4(+) T cells was largely IL-18Rα-dependent. Despite these findings however, IL-18Rα-deficient CD4(+) T cells induced comparable intestinal pathology to WT CD4(+) T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4(+) T cells is not critical for the development of T-cell-mediated colitis.
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Holmkvist
authors.affiliation: Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Lieneke
authors.initials: L
authors.lastname: Pool
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Hägerbrand
authors.affiliation: Immunology Section, Lund University, Lund, Sweden.|Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
authors.affiliation: Section of Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003092:Colitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007113:Immunity, Innate; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D053727:Interleukin-18 Receptor alpha Subunit / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053727:Interleukin-18 Receptor alpha Subunit; D017493:Leukocyte Common Antigens
keywords: IFN-γ; IL-18 receptor signaling; Innate responsiveness; T-cell transfer colitis