PMID- 22222225 OWN - NLM STAT- MEDLINE DCOM- 20120427 LR - 20211021 IS - 1525-2191 (Electronic) IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 180 IP - 3 DP - 2012 Mar TI - 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. PG - 984-997 LID - S0002-9440(11)01072-8 [pii] LID - 10.1016/j.ajpath.2011.11.009 [doi] AB - 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. CI - Copyright A(c) 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - McDonald, Keely G AU - McDonald KG AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Leach, Matthew R AU - Leach MR AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Brooke, Kaitlin W M AU - Brooke KWM AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Wang, Caihong AU - Wang C AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Wheeler, Leroy W AU - Wheeler LW AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Hanly, Elyse K AU - Hanly EK AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Rowley, Christopher W AU - Rowley CW AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. FAU - Levin, Marc S AU - Levin MS AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Medicine, St. Louis VA Medical Center, St. Louis, Missouri. FAU - Wagner, Michael AU - Wagner M AD - Department of Cell Biology, The State University of New York, Downstate Medical Center, Brooklyn, New York. FAU - Li, Ellen AU - Li E AD - Department of Internal Medicine, The State University of New York, Stony Brook, New York. FAU - Newberry, Rodney D AU - Newberry RD AD - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri. Electronic address: rnewberry@wustl.edu. LA - eng GR - R01 DK064798/DK/NIDDK NIH HHS/United States GR - R01 DK050446/DK/NIDDK NIH HHS/United States GR - P30-CA91842/CA/NCI NIH HHS/United States GR - R21 AI083538-02/AI/NIAID NIH HHS/United States GR - F32 DK085941/DK/NIDDK NIH HHS/United States GR - P30 CA091842/CA/NCI NIH HHS/United States GR - R21 AI083538/AI/NIAID NIH HHS/United States GR - DK064798/DK/NIDDK NIH HHS/United States GR - P30 DK052574/DK/NIDDK NIH HHS/United States GR - P30-DK52574/DK/NIDDK NIH HHS/United States GR - R01 DK064798-08/DK/NIDDK NIH HHS/United States GR - DK050446/DK/NIDDK NIH HHS/United States GR - DK085941/DK/NIDDK NIH HHS/United States GR - AI083538/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120102 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens, CD) RN - 0 (Immunoglobulin A) RN - 0 (Integrin alpha Chains) RN - 0 (Interleukin-6) RN - 0 (Isoenzymes) RN - 0 (Rbp2 protein, mouse) RN - 0 (Retinol-Binding Proteins, Cellular) RN - 0 (alpha E integrins) RN - 5688UTC01R (Tretinoin) RN - EC 1.2.1 (Aldehyde Dehydrogenase 1 Family) RN - EC 1.2.1.36 (ALDH1A1 protein, mouse) RN - EC 1.2.1.36 (Retinal Dehydrogenase) SB - IM MH - Aldehyde Dehydrogenase 1 Family MH - Animals MH - Antigens, CD/metabolism MH - Dendritic Cells/immunology/*metabolism MH - Immunity, Cellular/physiology MH - Immunoglobulin A/*biosynthesis MH - Integrin alpha Chains/metabolism MH - Interleukin-6/metabolism MH - Intestine, Small/cytology/immunology/*metabolism MH - Isoenzymes/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred Strains MH - Phenotype MH - Retinal Dehydrogenase/*metabolism MH - Retinol-Binding Proteins, Cellular/*metabolism MH - Tretinoin/*metabolism PMC - PMC3349881 EDAT- 2012/01/10 06:00 MHDA- 2012/04/28 06:00 PMCR- 2013/03/01 CRDT- 2012/01/07 06:00 PHST- 2011/06/17 00:00 [received] PHST- 2011/11/07 00:00 [revised] PHST- 2011/11/14 00:00 [accepted] PHST- 2012/01/07 06:00 [entrez] PHST- 2012/01/10 06:00 [pubmed] PHST- 2012/04/28 06:00 [medline] PHST- 2013/03/01 00:00 [pmc-release] AID - S0002-9440(11)01072-8 [pii] AID - AJPA717 [pii] AID - 10.1016/j.ajpath.2011.11.009 [doi] PST - ppublish SO - Am J Pathol. 2012 Mar;180(3):984-997. doi: 10.1016/j.ajpath.2011.11.009. Epub 2012 Jan 2.