Retinoic acid prevents mesenteric lymph node dendritic cells from inducing IL-13-producing inflammatory Th2 cells |
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Institution: | 1. Laboratory of Immunology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, Japan;2. JST, CREST, Tokyo, Japan;3. Institute of Neuroscience, Tokushima Bunri University, Kagawa, Japan;4. Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan;5. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan;6. Department of Biodefense Research, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan |
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Abstract: | The vitamin A (VA) metabolite retinoic acid (RA) affects the properties of T cells and dendritic cells (DCs). In VA-deficient mice, we observed that mesenteric lymph node (MLN)-DCs induce a distinct inflammatory T helper type 2 (Th2)-cell subset that particularly produces high levels of interleukin (IL)-13 and tumor necrosis factor-α (TNF-α). This subset expressed homing receptors for skin and inflammatory sites, and was mainly induced by B220?CD8α?CD11b+CD103? MLN-DCs in an IL-6- and OX40 ligand-dependent manner, whereas RA inhibited this induction. The corresponding MLN-DC subset of VA-sufficient mice induced a similar T-cell subset in the presence of RA receptor antagonists. IL-6 induced this subset differentiation from naive CD4+ T cells upon activation with antibodies against CD3 and CD28. Transforming growth factor-β inhibited this induction, and reciprocally enhanced Th17 induction. Treatment with an agonistic anti-OX40 antibody and normal MLN-DCs enhanced the induction of general inflammatory Th2 cells. In VA-deficient mice, proximal colon epithelial cells produced TNF-α that may have enhanced OX40 ligand expression in MLN-DCs. The repeated oral administrations of a T cell-dependent antigen primed VA-deficient mice for IL-13-dependent strong immunoglobulin G1 (IgG1) responses and IgE responses that caused skin allergy. These results suggest that RA inhibits allergic responses to oral antigens by preventing MLN-DCs from inducing IL-13-producing inflammatory Th2 cells. |
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