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. 2021 Feb 18;11:616483. doi: 10.3389/fimmu.2020.616483

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Copyright © 2021 Zou, Thornton, Chambers, Rosser and Ciurtin

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Vitamin D (both D₃and D₂) metabolic pathway and its physiological impact on immune cells. D₃ is synthesized from either 7-dehydrocholesterol from the skin via UVB activation or through the diet. D₂ is obtained from the diet. CYP2R1 enzyme converts D₃/D₂ to 25(OH)D₃/D₂ in the liver. CYP27B1 transforms 25(OH)D₃/D₂ into 1,25(OH)₂D₃/D₂ in the kidneys. 1,25(OH)₂D binds to VDR in immune cells which then bind to VDRE on genes to change gene expression. 1,25(OH)₂D can inhibit dendritic cell maturation, promote monocyte proliferation and differentiation into macrophages. It can also increase anti-inflammatory cytokines and the frequency of T_regs, as well as reduce pro-inflammatory Th1 cytokines. 1,25(OH)₂D can also reduce the ratio of CD4/CD8 and inhibit pro-inflammatory T cell differentiation and suppress antibody production by B cells.