title: Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion.
abstract: Dietary gluten influences the development of type 1 diabetes in nonobese diabetic (NOD) mice and biobreeding rats, and has been shown to influence a wide range of immunological factors in the pancreas and gut. In the present study, the effects of gluten on NK cells were studied in vitro and in vivo. We demonstrated that gliadin increased direct cytotoxicity and IFN-γ secretion from murine splenocytes and NK cells toward the pancreatic beta-cell line MIN6 cells. Additionally, stimulation of MIN6 cells led to a significantly increased proportion of degranulating C57BL/6 CD107a(+) NK cells. Stimulation of C57BL/6 pancreatic islets with gliadin significantly increased secretion of IL-6 more than ninefold. In vivo, the gluten-containing diet led to a higher expression of NKG2D and CD71 on NKp46(+) cells in all lymphoid organs in BALB/c and NOD mice compared with the gluten-free diet. Collectively, our data suggest that dietary gluten increases murine NK-cell activity against pancreatic beta cells. This mechanism may contribute to development of type 1 diabetes and explain the higher disease incidence associated with gluten intake in NOD mice.
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Larsen
authors.forename: Morten
authors.initials: M
authors.lastname: Dall
authors.forename: Julie Christine
authors.initials: JC
authors.lastname: Antvorskov
authors.forename: Christian
authors.initials: C
authors.lastname: Weile
authors.forename: Kåre
authors.initials: K
authors.lastname: Engkilde
authors.forename: Knud
authors.initials: K
authors.lastname: Josefsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005983:Glutens / Q000276:immunology* / Q000633:toxicity*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD
chemical_list: D016207:Cytokines; D005983:Glutens
keywords: C56BL/6 mice; Gliadin; Gluten; NK cells; NOD mice; Type 1 diabetes