Document Detail


Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation.
MedLine Citation:
PMID:  23322377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jinsam Chang; Shankar Thangamani; Myung H Kim; Benjamin Ulrich; Sidney M Morris; Chang H Kim
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-14
Journal Detail:
Title:  European journal of immunology     Volume:  43     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-17     Completed Date:  2013-06-12     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  967-78     Citation Subset:  IM    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginase / genetics,  metabolism*
Binding Sites
Cell Differentiation / immunology*
Dendritic Cells / drug effects*,  immunology*,  metabolism
Forkhead Transcription Factors / metabolism
Gene Expression Regulation / drug effects
Interleukin-4 / pharmacology
Mice
Mice, Knockout
Promoter Regions, Genetic
Receptors, Retinoic Acid / metabolism
T-Lymphocyte Subsets / cytology*,  immunology*,  metabolism
T-Lymphocytes, Regulatory / cytology,  immunology,  metabolism
Tretinoin / pharmacology*
Grant Support
ID/Acronym/Agency:
R01 AI074745/AI/NIAID NIH HHS; R01 AI080769/AI/NIAID NIH HHS; R01 DK076616/DK/NIDDK NIH HHS; R01AI074745/AI/NIAID NIH HHS; R01DK076616/DK/NIDDK NIH HHS; R01GM57384/GM/NIGMS NIH HHS; R21 AI063064/AI/NIAID NIH HHS; R56 AI080769/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Receptors, Retinoic Acid; 207137-56-2/Interleukin-4; 5688UTC01R/Tretinoin; EC 3.5.3.1/Arg1 protein, mouse; EC 3.5.3.1/Arginase
Comments/Corrections

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