Immunoregulatory effects of vitamin D3 in experimentally induced type 1 diabetes

Abstract

The mechanism underlying the impairment of the function of the cellular component of the immune response and its regulation by vitamin D³ in diabetes mellitus remains incompletely characterized. The present study addresses the specific features of the functioning of the T-cell link of immune response and the humoral response to injecyion of an artificial antigen in a diabetes model and after prolonged administration of vitamin D³. Chronic hyperglycemia occurring in diabetes induced a 2.3-fold decrease of the content of the marker substance 25OHD³, the major precursor of hormonally active forms of vitamin D³, in the serum. The development of vitamin D³ deficiency is accompanied by an impairment of the proliferative activity of T cells and a change in relative numbers of regulatory (CD4⁺) and cytotoxic (CD8⁺) lymphocytes. An increase of the content of the phosphorylated p65 subunit of the nuclear factor κB and more intensive translocation of this protein to the nucleus were detected in total lysates of T lymphocytes from the spleen. Moreover, enhancement of the humoral IgG response to intraperitoneal administration of a recombinant B subunit of diphtheria toxin was demonstrated. Impairment of the cellular component of the immune response was accompanied by increased apoptotic death of splenocytes, as is evident from the increased binding of the Annexin V-GFP tag to phosphatidyl serine residues exposed on the external side of the plasmalemma during apoptosis. Prolonged administration of vitamin D₃ (during 2 months; dose 20 IU) promoted the normalization of proliferative activity and the relative size of T-cell subpopulations, led to a decrease of the content of the phosphorylated p65 subunit of NF-κB, and improved the balance of the secretion of IgG targeting the artificial antigen in diabetic animals. These changes were accompanied by a decrease in the number of apoptotic events in the entire splenocyte population. The results of the present study demonstrate the important role of vitamin D₃ in the regulation of the functions of the immune system in type 1 diabetes.