title: γδ T Cells Coexpressing Gut Homing α4β7 and αE Integrins Define a Novel Subset Promoting Intestinal Inflammation.
abstract: γδ T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. In this study, we identified a unique γδ T cell subset that coexpresses high levels of gut-homing integrins, CD103 and α4β7. They were exclusively found in the mesenteric lymph node after T cell-mediated colitis induction, and their appearance preceded the inflammation. Adoptive transfer of the CD103+α4β7highsubsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity. The level of generation correlated with the disease severity. Moreover, these cells were also found to be elevated in a spontaneous mouse model of ileitis. Based on the procolitogenic function, we referred to this subset as "inflammatory" γδ T cells. Targeting inflammatory γδ T cells may open a novel strategy to treat inflammatory diseases where γδ T cells play a pathogenic role including inflammatory bowel disease.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Jeong-Su
authors.initials: JS
authors.lastname: Do
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Sohee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Karen
authors.identifier: 0000-0001-8609-4797
authors.initials: K
authors.lastname: Keslar
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Eunjung
authors.identifier: 0000-0001-5753-0385
authors.initials: E
authors.lastname: Jang
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195; and.
authors.forename: Emina
authors.identifier: 0000-0003-2495-4370
authors.initials: E
authors.lastname: Huang
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fairchild
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44116.
authors.forename: Theresa T
authors.initials: TT
authors.lastname: Pizarro
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195; minb@ccf.org.
authors.forename: Booki
authors.identifier: 0000-0002-2151-9413
authors.initials: B
authors.lastname: Min
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology*; D016023:Integrins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D059467:Transcriptome
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing; C091367:alpha E integrins; C071777:integrin alpha4beta7