![]() Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. 1α,25-dihydroxyvitamin D3 transrepresses retinoic acid transcriptional activity via vitamin D receptor in myeloid cells. ![]() This paper shows that CD103 + DCs from mesenteric lymph nodes induce T Reg cells by a mechanism involving TGF β and retinoic acid. A functionally specialized population of mucosal CD103 + DCs induces Foxp3 + regulatory T cells via a TGF-β- and retinoic acid-dependent mechanism. It is also shown that gut-associated DCs can metabolize dietary vitamin A into retinoic acid, which explains their capacity to imprint gut-homing lymphocytes.Ĭoombes, J. This paper reports for the first time that retinoic acid is necessary and sufficient to induce gut-homing receptors on T cells. Retinoic acid imprints gut-homing specificity on T cells. Metabolism of vitamin A and its active metabolite all-trans-retinoic acid in small intestinal enterocytes. ![]() Design of selective nuclear receptor modulators: RAR and RXR as a case study. Delivery of retinoid-based therapies to target tissues. Overview of retinoid metabolism and function. Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and transcriptional regulation by 1α, 25-dihydroxyvitamin D3. Regulation of 25-hydroxyvitamin D3–1α-hydroxylase and production of 1α, 25-dihydroxyvitamin D3 by human dendritic cells. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. This paper reports that 1,25(OH) 2 VD 3 is synthesized by dermal DCs and induces CCR10 expression by human T cells, presumably increasing their epidermotropism. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion. Effect of vitamins A and E on ischemia-reperfusion damage in rabbit heart. Influence of vitamin C on the metabolism of arachidonic acid and the development of aortic lesions during experimental atherosclerosis in rabbits. ![]() Challenges and opportunities in the translation of the science of vitamins. Given its potent immunomodulatory properties, 1,25(OH) 2VD 3 analogues are currently being tested in autoimmune diseases and as adjuvants for immunosuppressive therapy in transplantation. Retinoic acid is also involved in the differentiation of IgA-secreting B cells in the gut. Conversely, retinoic acid blocks the upregulation of skin-homing receptors. Retinoic acid is synthesized by gut-associated DCs and induces the expression of gut-homing receptors α 4β 7-integrin and CC-chemokine receptor 9 (CCR9) by lymphocytes following activation. It also inhibits T H17-cell differentiation and, reciprocally, potentiates T Reg-cell development. The vitamin A metabolite retinoic acid induces T H2-cell responses. By contrast, 1,25(OH) 2VD 3 enhances the bactericidal capacity of macrophages. Part of this effect might be indirect by decreasing T-cell help.ġ,25(OH) 2VD 3 modulates dendritic cell (DC) function by impairing their maturation and enhancing their capacity to generate T R1 cells. It also decreases T H17-cell differentiation, with reciprocal upregulation of forkhead box protein 3 (FOXP3) + regulatory T (T Reg) cells and T regulatory type 1 (T R1) cells.ġ,25(OH) 2VD 3 also inhibits the proliferation of B cells and their differentiation into antibody-secreting cells. The vitamin D metabolite 1,25(OH) 2VD 3 inhibits T-helper 1 (T H1)- and enhances T H2-cell responses. The metabolites of vitamins A and D, retinoic acid and 1,25(OH) 2VD 3, respectively, bind to nuclear receptors and exert potent and specific immunomodulatory effects.
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