IL-4 and retinoic acid synergistically induce regulatory dendritic cells expressing Aldh1a2.
IL-4 and retinoic acid synergistically induce regulatory dendritic cells expressing Aldh1a2.
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DOI：
10.4049/jimmunol.1300329
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发表时间：
2013-09-15
期刊：
影响因子：
--
通讯作者：
Khoury SJ
中科院分区：
文献类型：
--
作者：
Zhu B;Buttrick T;Bassil R;Zhu C;Olah M;Wu C;Xiao S;Orent W;Elyaman W;Khoury SJ
While activated inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs) are potent T cell suppressors, non-activated IMCs and IDCs promote T cell activation and T helper (Th) 1/Th17 cell differentiation. In this study, we investigated how to reduce the pro-inflammatory properties of IMCs and IDCs, and convert them into immune regulatory DCs. We found that interleukin (IL)-4 and retinoic acid (RA) treatment of GM-CSF-differentiated IDCs synergistically induced the expression of aldehyde dehydrogenase family1 subfamily A2 (Aldh1a2), a rate-limiting enzyme for RA synthesis in DCs. IL-4+RA-treated IDCs upregulated CD103 expression and markedly reduced the production of pro-inflammatory cytokines upon activation. IL-4+RA-treated IDCs strongly induced CD4+Foxp3+ regulatory T cell (Treg) differentiation and suppressed Th1 and Th17 differentiation. Mechanistically, the transcription factors Stat6 and RARβ play important roles in Aldh1a2 induction. In addition, IL-4 and RA signaling pathways interact closely to enhance the regulatory function of treated DCs. Adoptive transfer of IL-4+RA-treated DCs significantly increased Treg frequency in vivo. Direct treatment with IL-4 and RA also markedly suppressed actively induced EAE. Our data demonstrate the synergistic effect of IL-4 and RA in inducing a regulatory phenotype in IDCs, providing a potential treatment strategy for autoimmune diseases.
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