Poster Presentation 6th Australian Health and Medical Research Congress 2012

Immunosuppressive effects of Vitamin D3 on IgE + specific Ag-mediated mast cells (#338)

Natasha Kolesnikoff 1 , Chunping Yu 1 2 , Kwok Ho Yip 1 , Houng Taing 1 2 , Lisa Biggs 1 , Alicia Chenoweth 1 2 , Paul H Anderson 3 , Michael Samuel 1 2 , Angel Lopez 1 , Michele A Grimbaldeston 1 2
  1. Centre for Cancer Biology, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia
  2. School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, Australia
  3. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia

Mast cells (MCs) are typically regarded as pro-inflammatory effecter cells in immunoglobulin (Ig)E-dependent allergic disorders. However, MCs can have anti-inflammatory properties in response to application of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the biologically active form of vitamin D3 (VitD3). In the presence of 1α,25(OH)2D3, IgE + specific Ag (sAg)-stimulation in bone marrow-derived MCs (BMCMCs) resulted in a suppressed production of pro-inflammatory cytokines, TNF and IL-6, in a vitamin D receptor (VDR)-dependent manner. Moreover, the presence of 1α,25(OH)2D3 can induce the production of anti-inflammatory cytokine IL10 from mouse BMCMCs. In addition, we have shown that mouse BMCMCs have the ability to produce 1α,25(OH)2D3 from the inactive VitD3 metabolite, 25-hydroxyvitamin D3 (25OHD3), due to expression and activity of the hydroxylase enzyme CYP27B1. By employing a mouse IgE-mediated MC-dependent passive cutaneous anaphylaxis (PCA) model as well as four mouse groups with different cutaneous MC profiles in the ears, including WT mice, MC-deficient C57BL/6-KitW-sh/W-sh mice and C57BL/6-KitW-sh/W-sh mice engrafted with either WT or VDR-/- BMCMCs, we found that topical application of 1α,25(OH)2D3 or 25OHD3 significantly reduced the magnitude of PCA-associated ear swelling. Taken together, these effects required the presence of VDR-expressing dermal MCs. Our findings provide evidence that 1α,25(OH)2D3, as well as 25OHD3, can suppress IgE + sAg-mediated MC activation in a VDR-dependent manner both in vitro and in vivo, and suggest that 1α,25(OH)2D3 may have therapeutic potential for treatment of MC-dependent IgE-associated allergic disorders.