title: CD151 Regulates T-Cell Migration in Health and Inflammatory Bowel Disease.
abstract: The continuous recirculation of mature lymphocytes and their entry into the peripheral lymph nodes are crucial for the development of an immune response to foreign antigens. Occasionally, the entry and the subsequent response of T lymphocytes in these sites lead to severe inflammation and pathological conditions. Here, we characterized the tetraspanin molecule, CD151, as a regulator of T cell motility in health and in models of inflammatory bowel disease. CD151 formed a cell surface complex with VLA-4 and LFA-1 integrins, and its activation led to enhanced migration of T cells. Picomolar levels of CCL2 that were previously shown to inhibit T-cell migration to lymph nodes suppressed CD151 expression and dissociated CD151-integrin complexes in T lymphocytes, resulting in attenuated migration toward T-cell attractant chemokines. To directly inhibit CD151 function, a truncated CD151 peptide fragment mimicking of the CD151 extracellular loop was designed. CD151 extracellular loop inhibited T-cell migration in vitro and in vivo and attenuated the development of dextrane sulfate sodium-induced colitis. Thus, CD151 is a key orchestrator of T cell motility; interference with its proper function results in attenuated progression of inflammatory bowel disease.
authors.affiliation: *Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; ‡IBD Unit, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Israel (affiliated with the Sackler Faculty of Medicine, Tel Aviv, Israel); and §Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Einat
authors.initials: E
authors.lastname: Zelman-Toister
authors.forename: Eszter
authors.initials: E
authors.lastname: Bakos
authors.forename: Sivan
authors.initials: S
authors.lastname: Cohen
authors.forename: Ehud
authors.initials: E
authors.lastname: Zigmond
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Adi
authors.initials: A
authors.lastname: Sagiv
authors.forename: Gili
authors.initials: G
authors.lastname: Hart
authors.forename: Nathali
authors.initials: N
authors.lastname: Kaushansky
authors.forename: Avi
authors.initials: A
authors.lastname: Ben-Nun
authors.forename: Nitsan
authors.initials: N
authors.lastname: Maharshak
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
authors.forename: Shirly
authors.initials: S
authors.lastname: Becker-Herman
authors.forename: Idit
authors.initials: I
authors.lastname: Shachar
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology* / Q000502:physiology; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011379:Prognosis; D054390:Receptors, CCR2 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D060185:Tetraspanin 24 / Q000502:physiology*
chemical_list: C515335:Ccr2 protein, mouse; C554716:Cd151 protein, mouse; D018398:Homeodomain Proteins; D054390:Receptors, CCR2; D060185:Tetraspanin 24; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse