Acute erythemal ultraviolet radiation causes systemic immunosuppression in the absence of increased 25-hydroxyvitamin D3 levels in male mice

PLoS One. 2012;7(9):e46006. doi: 10.1371/journal.pone.0046006. Epub 2012 Sep 26.

Abstract

Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator of the immunosuppression that occurs following UV radiation (UVR) exposure. Both UVR and vitamin D drive immune responses towards tolerance by ultimately increasing the suppressive activities of regulatory T cells. To examine a role for UVR-induced vitamin D, vitamin D(3)-deficient mice were established by dietary vitamin D(3) restriction. In comparison to vitamin D(3)-replete mice, vitamin D(3)-deficient mice had significantly reduced serum levels of 25-hydroxyvitamin D(3) (25(OH)D(3), <20 nmol.L(-1)) and 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), <20 pmol.L(-1)). Following either acute erythemal UVR, or chronic sub-erythemal UVR (8 exposures over 4 weeks) treatment, serum 25(OH)D(3) levels significantly increased in vitamin D(3)-deficient female but not male mice. To determine if UVR-induced vitamin D was a mediator of UVR-induced systemic immunosuppression, responses were measured in mice that were able (female) or unable (male) to increase systemic levels of 25(OH)D(3) after UVR. Erythemal UVR (≥ 4 kJ/m(2)) suppressed contact hypersensitivity responses (T helper type-1 or -17), aspects of allergic airway disease (T helper type-2) and also the in vivo priming capacity of bone marrow-derived dendritic cells to a similar degree in female and male vitamin D(3)-deficient mice. Thus, in male mice, UVR-induced 25(OH)D(3) is not essential for mediating the immunosuppressive effects of erythemal UVR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bone Marrow Cells / cytology
  • Bronchoalveolar Lavage
  • Calcifediol / metabolism
  • Calcium / metabolism
  • Dendritic Cells / cytology
  • Dose-Response Relationship, Radiation
  • Erythema / metabolism*
  • Female
  • Immune Tolerance / drug effects
  • Immunosuppression / methods*
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Skin / metabolism
  • Ultraviolet Rays*
  • Vitamin D / metabolism

Substances

  • Immunosuppressive Agents
  • Vitamin D
  • Calcifediol
  • Calcium

Grant support

This study was supported by grants from the National Health and Medical Research Council of Australia (#458612, PHH), the Cancer Council of Western Australia (#1008985, PHH and SG), the Asthma Foundation of Western Australia (SG and PHH), the Raine Foundation (SG and PHH), and the BrightSpark Foundation (SG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.