title: Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses.
abstract: Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)(2)D(3) to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)(2)D(3) treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)(2)D(3)-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)(2)D(3)-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)(2)D(3) suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Natasha R
authors.initials: NR
authors.lastname: Ryz
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Patterson
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Caixia
authors.initials: C
authors.lastname: Ma
authors.forename: Tina
authors.initials: T
authors.lastname: Huang
authors.forename: Ganive
authors.initials: G
authors.lastname: Bhinder
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wu
authors.forename: Justin
authors.initials: J
authors.lastname: Chan
authors.forename: Alexa
authors.initials: A
authors.lastname: Glesby
authors.forename: Ho Pan
authors.initials: HP
authors.lastname: Sham
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dutz
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
authors.forename: Kevan
authors.initials: K
authors.lastname: Jacobson
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000009:adverse effects*; D044082:Citrobacter rodentium / Q000187:drug effects / Q000276:immunology*; D004198:Disease Susceptibility / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004756:Enterobacteriaceae Infections / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D016867:Immunocompromised Host / Q000187:drug effects / Q000276:immunology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D002117:Calcitriol