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Adaptive immunity (cancer, viruses, autoimmune) and vitamin D – April 2016

Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer.

Crit Rev Clin Lab Sci. 2016 Apr;53(2):132-45. doi: 10.3109/10408363.2015.1094443. Epub 2015 Oct 19.
Sarkar S1,2, Hewison M3, Studzinski GP4, Li YC5, Kalia V1,2.
1a Department of Pediatrics, Division of Hematology and Oncology , University of Washington School of Medicine , Seattle , WA , USA .
2b Seattle Children's Research Institute, Ben Towne Center for Childhood Cancer Research , Seattle , WA , USA .
3c Centre for Endocrinology, Diabetes and Metabolism (CEDAM), The University of Birmingham , Birmingham , UK .
4d Department of Pathology and Laboratory Medicine , Rutgers New Jersey Medical School , Newark , NJ , USA , and.
5e Department of Medicine, Division of Biological Sciences , The University of Chicago , Chicago , IL , USA.

The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome.
While much is known about the effects of vitamin D on innate immune responses and helper T (TH) cell immunity, there has been relatively limited progress on the frontier of cytotoxic T lymphocyte (CTL) immunity - an arm of host cellular adaptive immunity that is crucial for the control of such intracellular pathogens as

  • human immunodeficiency virus (HIV),
  • tuberculosis (TB),
  • malaria, and
  • hepatitis C virus (HCV).

In this review, we discuss the strong historical and clinical link between vitamin D and infectious diseases that involves cytotoxic T lymphocyte (CTL) immunity, present our current understanding as well as critical knowledge gaps in the realm of vitamin D regulation of host CTL responses, and highlight potential regulatory connections between vitamin D and effector and memory CD8 T cell differentiation events during infections.

PMID: 26479950

Publisher wants $54 for the PDF
Notes after purchase and quick read by VitaminDWiki
15 pages, Very technical
Great summary chart of adaptive immune system and vitamin D

  • Summary table of 38 possible genes involved - including Vitamin D Receptor
    VDR Reference: Sarkar S, Kalia V, Haining WN, et al. Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J Exp Med 2008;205:625–40.
  • "In the case of dengue infections, VDR gene polymorphisms have been identified as predictors of hemorrhagic fever and shock"
    Reference: Alagarasu K, Honap T, Mulay AP, et al. Association of vitamin D receptor gene polymorphisms with clinical outcomes of dengue virus infection. Hum Immunol 2012;73:1194–9.
    Abstract: Vitamin D is known to affect pathogenesis of dengue through modulation of immune responses. Vitamin D exerts its effects through vitamin D receptor (VDR). The functioning of VDR is affected by the gene polymorphisms in the coding (rs2228570) and 3'untranslated region (UTR) (rs1544410, rs7975232 and rs731236).
    In the present study, VDR gene polymorphisms were investigated in 112 dengue infected patients (83 dengue fever (DF) and 29 dengue hemorrhagic fever cases (DHF)) and 105 apparently healthy controls (HCs) using polymerase chain reaction based restriction fragment length polymorphisms methods. HCs had no documented evidence of symptomatic dengue. Results revealed significantly lower frequency of 'C' allele of rs7975232 in all dengue patients (DEN) as compared to HCs [(P corrected (Pc)=0.014, Odds ratio (OR) 0.51]. The frequency of C/C genotype of rs7975232 was significantly lower in DEN and DF cases compared to HCs (DEN vs. HCs: Pc=0.0184, OR 0.24; DF cases vs. HCs: Pc=0.028, OR 0.21). The frequency of T allele of rs2228570 in a dominant mode was significantly higher in DHF cases as compared to DF cases (P=0.034 OR 2.58). A significantly lower frequency of the haplotype G-C-T (Pc=0.0135) and higher frequency of the haplotype G-A-T (Pc=0.000085) was observed in DEN and DF cases as compared to HCs. The results suggest that the 3'UTR haplotypes of VDR gene are differentially associated with risk of symptomatic dengue requiring hospitalization. The 'T' allele of rs2228570 polymorphism in a dominant mode of inheritance is associated with DHF.