| Epithelial expression of the cytosolic retinoid chaperone cellular retinol binding protein II is essential for in vivo imprinting of local gut dendritic cells by lumenal retinoids. | |
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MedLine Citation:
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PMID: 22222225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dendritic cells (DCs) use all-trans retinoic acid (ATRA) to promote characteristic intestinal responses, including Foxp3(+) Treg conversion, lymphocyte gut homing molecule expression, and IgA production. How this ability to generate ATRA is conferred to DCs in vivo remains largely unstudied. Here, we observed that among DCs, retinaldehyde dehydrogenase (ALDH1), which catalyzes the conversion of retinal to ATRA, was preferentially expressed by small intestine CD103(+) lamina propria (LP) DCs. Retinoids induced LP CD103(+) DCs to generate ATRA via ALDH1 activity. Either biliary or dietary retinoids were required to confer ALDH activity to LP DCs in vivo. Cellular retinol-binding protein II (CRBPII), a cytosolic retinoid chaperone that directs enterocyte retinol and retinal metabolism but is redundant to maintain serum retinol, was required to confer ALDH activity to CD103(+) LP DCs. CRBPII expression was restricted to small intestine epithelial cells, and ALDH activity in CRBPII(-/-) DCs was restored by transfer to a wild-type recipient. CD103(+) LP DCs from CRBPII(-/-) mice had a decreased capacity to promote IgA production. Moreover, CD103(+) DCs preferentially associated with the small intestine epithelium and LP CD103(+) DC ALDH activity, and the ability to promote IgA production was reduced in mice with impaired DC-epithelia associations. These findings demonstrate in vivo roles for the expression of epithelial CRBPII and lumenal retinoids to imprint local gut DCs with an intestinal phenotype. |
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Authors:
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Keely G McDonald; Matthew R Leach; Kaitlin W M Brooke; Caihong Wang; Leroy W Wheeler; Elyse K Hanly; Christopher W Rowley; Marc S Levin; Michael Wagner; Ellen Li; Rodney D Newberry |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-02 |
Journal Detail:
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Title: The American journal of pathology Volume: 180 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-20 Completed Date: 2012-04-27 Revised Date: 2012-05-14 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 984-97 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / metabolism Dendritic Cells / immunology, metabolism* Immunity, Cellular / physiology Immunoglobulin A / biosynthesis* Integrin alpha Chains / metabolism Interleukin-6 / metabolism Intestine, Small / cytology, immunology, metabolism* Isoenzymes / metabolism* Mice Mice, Inbred C57BL Mice, Inbred Strains Phenotype Retinal Dehydrogenase / metabolism* Retinol-Binding Proteins, Cellular / metabolism* Tretinoin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI083538/AI/NIAID NIH HHS; DK050446/DK/NIDDK NIH HHS; DK064798/DK/NIDDK NIH HHS; DK085941/DK/NIDDK NIH HHS; P30-CA91842/CA/NCI NIH HHS; P30-DK52574/DK/NIDDK NIH HHS; R01 DK064798-08/DK/NIDDK NIH HHS; R21 AI083538-02/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Immunoglobulin A; 0/Integrin alpha Chains; 0/Interleukin-6; 0/Isoenzymes; 0/Rbp2 protein, mouse; 0/Retinol-Binding Proteins, Cellular; 0/alpha E integrins; 302-79-4/Tretinoin; EC 1.2.1.-/aldehyde dehydrogenase 1; EC 1.2.1.36/Retinal Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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