Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, College of Veterinary Medicine Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
Eur J Immunol. 2013 Apr;43(4):967-78. doi: 10.1002/eji.201242772. Epub 2013 Feb 14.
Arginase I (Arg1), an enzyme expressed by many cell types including myeloid cells, can regulate immune responses. Expression of Arg1 in myeloid cells is regulated by a number of cytokines and tissue factors that influence cell development and activation. Retinoic acid, produced from vitamin A, regulates the homing and differentiation of lymphocytes and plays important roles in the regulation of immunity and immune tolerance. We report here that optimal expression of Arg1 in DCs requires retinoic acid. Induction of Arg1 by retinoic acid is directly mediated by retinoic acid-responsive elements in the 5' noncoding region of the Arg1 gene. Arg1, produced by DCs in response to retinoic acid, promotes the generation of FoxP3(+) regulatory T (Treg) cells. Importantly, blocking the retinoic acid receptor makes DCs hypo-responsive to known inducers of Arg1 such as IL-4 and GM-CSF in Arg1 expression. We found that intestinal CD103(+) DCs that are known to produce retinoic acid highly express Arg1. Our results establish retinoic acid as a key signal in expression of Arg1 in DCs.
精氨酸酶 I（Arg1）是一种由多种细胞类型（包括髓样细胞）表达的酶，可调节免疫反应。髓样细胞中 Arg1 的表达受许多影响细胞发育和激活的细胞因子和组织因子调节。维生素 A 产生的视黄酸调节淋巴细胞的归巢和分化，并在调节免疫和免疫耐受方面发挥重要作用。我们在这里报告，树突状细胞（DCs）中 Arg1 的最佳表达需要视黄酸。视黄酸通过 Arg1 基因 5'非编码区中的视黄酸反应元件直接介导 Arg1 的诱导。DCs 产生的 Arg1 促进 FoxP3(+)调节性 T（Treg）细胞的生成。重要的是，阻断视黄酸受体使 DCs 对 Arg1 的已知诱导剂（如 IL-4 和 GM-CSF）的 Arg1 表达反应降低。我们发现，已知产生视黄酸的肠道 CD103(+)DCs高度表达 Arg1。我们的结果确立了视黄酸作为 DCs 中 Arg1 表达的关键信号。
