Vitamin D levels do not predict the stage of hepatic fibrosis in patients with non-alcoholic fatty liver disease: A PRISMA compliant systematic review and meta-analysis of pooled data

Figure 1 The immunomodulatory effects of 1,25(OH)₂D₃. 1,25(OH)₂D₃ targets different players of the innate and adaptive immune compartment. 1,25(OH)₂D₃ stimulates innate immune responses by enhancing the chemotactic and phagocytotic responses of macrophages, as well as the production of antimicrobial proteins such as cathelicidin. On the other hand, 1,25(OH)₂D₃ also modulates adaptive immunity. At the level of the APC (like the DC), 1,25(OH)₂D₃ inhibits the surface expression of the MHC-II-complexed antigen and co-stimulatory molecules, in addition to the production of the cytokines IL-12 and IL-23, thereby indirectly shifting the polarization of T cells from a Th1 and Th17 phenotype towards a Th2 phenotype. In addition, 1,25(OH)₂D₃ directly affects T cell responses, by inhibiting the production of Th1 cytokines (IL-2 and IFN-γ) and Th17 cytokines (IL-17 and IL-21), and by stimulating Th2 cytokine production (IL-4). Moreover, 1,25(OH)₂D₃ favors Treg cell development via modulation of DCs and by directly targeting T cells. Finally, 1,25(OH)₂D₃ blocks plasma cell differentiation, IgG and IgM production, and B cell proliferation. Reproduced with the permission of the Nature Publishing Group[52].