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. 2018 Dec 6;9:2853. doi: 10.3389/fimmu.2018.02853

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Copyright © 2018 Chen and Mayne.

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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Chronic GVHD and vitamins A and D. cGVHD pathogenesis involves: (1) Early inflammation and tissue injury. An existing inflammation and danger signals activate innate immune cells and recruits donor T cells to the tissue. (2) Dysregulated immunity with loss of tolerance. Activated CD4 T cells stimulate the maturation of auto-reactive B cells. (3) Mature B cells produce various autoantibodies against host antigens. (4) Aberrant tissue repair and fibrosis via macrophages and fibroblasts. Tr1/Treg play immunomodulatory roles in chronic GVHD pathogenesis. It has been reported that synthetic retinoid (shown in green) reduces cGVHD by inhibiting Th1 and Th17 cells. It may also facilitate the generation of Tr1/Tregs. The potential effects of vitamin D on cGVHD (shown in orange) may include positive effects on Tr1/Treg function and polarization as well as inhibitory effects on proinflammatory T cell polarization, inflammatory cytokines, autoantibody secretion and collagen production. This figure is adapted from Cooke et al. (12).