Immunological role of vitamin D at the maternal–fetal interface
- 1College of Medical and Dental Sciences, Centre for Women's and Children's Health
2College of Medical and Dental Sciences, Centre of Endocrinology, Diabetes and Metabolism (CEDAM), University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
3Departments of Pediatrics, Biochemistry, and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
4Reproductive and Vascular Biology Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
5Fetal Medicine Centre, Birmingham Women's Foundation Trust, Birmingham B15 2TG, UK
- Correspondence should be addressed to J A Tamblyn; Email: j.tamblyn{at}bham.ac.uk
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Figure 1
Proposed immunomodulatory effects of vitamin D at the maternal–fetal interface. Illustration of both the innate and adaptive leukocyte decidual subsets with the potential capacity for intrinsic 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis from 25-hydroxyvitamin D (25OHD), including uterine NK cells (uNK), macrophages, dendritic cells (DCs), T cells and B cells. Their postulated pro-tolerogenic effects specifically at the fetal–maternal interface, in the presence of 1,25(OH)2D, are illustrated. Notably, uNK cells predominate and demonstrate reduced cytotoxic potential. ‘M1’ macrophage subtypes exist, demonstrating enhanced antibacterial, pro-inflammatory actions in the presence of 1,25(OH)2D. However, the pro-tolerogenic ‘M2’ subsets predominate, displaying both enhanced proliferative and tissue remodelling capacities. Immature DCs are sparse; 1,25(OH)2D may augment their reduced capacity for antigen presentation and enhanced expression of anti-inflammatory cytokines, such as IL10. Immunosuppressive CD8+ and CD4+ T cells coexist and they are suspected key producers of 1,25(OH)2D. Postulated pro-tolerogenic effects include a shift from a Th1 to a Th2 phenotype, increased T regulatory cell (Treg) production and suppression of T helper 17 cell (Th17) activity. Finally, albeit infrequent in number, B cell proliferation and differentiation may be inhibited in the presence of 1,25(OH)2D. 1,25D, 1,25(OH)2D; 25D, 25OHD; M, macrophage; DC, dendritic cell; HLA, human leukocyte antigen; Ig, immunoglobulin; IL, interleukin; 25OHD, 25-hydroxyvitamin D; 1,25(OH)2D, 1,25-dihydroxyvitamin D; VDR, vitamin D receptor; uNK, uterine natural killer cell; Th, T helper cell; Treg, T Regulatory cell; CD, cluster of differentiation; Ag, antigen; IFNγ, interferon gamma; TNFα, tumour necrosis factor alpha.
- © 2015 Society for Endocrinology
