title: Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation.
abstract: 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.
authors: 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.
authors: Jinsam
authors: J
authors: Chang
authors: Shankar
authors: S
authors: Thangamani
authors: Myung H
authors: MH
authors: Kim
authors: Benjamin
authors: B
authors: Ulrich
authors: Sidney M
authors: SM
authors: Morris
authors: Chang H
authors: CH
authors: Kim
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018168:Receptors, Retinoic Acid; D015847:Interleukin-4; D014212:Tretinoin; C544448:Arg1 protein, mouse; D001119:Arginase