title: CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.
abstract: Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Brasseit
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Althaus-Steiner
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Faderl
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Dickgreber
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Saurer
authors.affiliation: Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Genitsch
authors.affiliation: Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Dolowschiak
authors.affiliation: Maurice E. Müller Laboratories, University Clinic for Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Developmental Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Finke
authors.affiliation: Institute of Microbiology, ETH Zürich, Zurich, Switzerland.
authors.forename: W-D
authors.initials: WD
authors.lastname: Hardt
authors.affiliation: Maurice E. Müller Laboratories, University Clinic for Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
authors.forename: K D
authors.initials: KD
authors.lastname: McCoy
authors.affiliation: Maurice E. Müller Laboratories, University Clinic for Visceral Surgery and Medicine, University of Bern, Bern, Switzerland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Macpherson
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Corazza
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Noti
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Mueller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002465:Cell Movement; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000276:immunology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing
chemical_list: D014409:Tumor Necrosis Factor-alpha