Lack of Retinoic Acid Leads to Increased Langerin-Expressing Dendritic Cells in Gut-Associated Lymphoid Tissues

Title
Lack of Retinoic Acid Leads to Increased Langerin-Expressing Dendritic Cells in Gut-Associated Lymphoid Tissues
Author(s)
장재훈Sun-Young Chang[Sun-Young Chang]Hye-Ran Cha[Hye-Ran Cha]Hyun-Jeong Ko[Hyun-Jeong Ko]Hyungjun Yang[Hyungjun Yang]Bernard Malissen[Bernard Malissen]Makoto Iwata[Makoto Iwata]Mi-Na Kweon[Mi-Na Kweon]
Keywords
T-CELLS; BIRBECK GRANULES; LAMINA PROPRIA; STEADY-STATE; IN-VIVO; DIFFERENTIATION; RECEPTOR; SKIN; CCR7; GENERATION
Issue Date
201004
Publisher
W B SAUNDERS CO-ELSEVIER INC
Citation
GASTROENTEROLOGY, v.138, no.4, pp.1468 - U332
Abstract
BACKGROUND & AIMS: Retinoic acid (RA) is a crucial factor for maintaining homeostasis in the gut, including lymphocyte homing, immunoglobulin (Ig) A production, and T regulatory cells (Treg) and T helper cell 17 (T(H)17) generation. Until now, most attention has focused on the function of dendritic cells (DCs) to initiate adaptive immunity including T and B lymphocytes through RA. To investigate the effects of RA on DCs of gut-associated lymphoid tissue (GALT), we analyzed the phenotype and function of DC subsets from GALT of vitamin A-deficient (VAD) mice. METHOD: VAD mice were prepared by feeding them a VAD diet over 12 weeks from gestational days 10-14. RESULTS: Here, we report that tremendous increase of langerin(+) DCs occurred in the mesenteric lymph nodes (MLNs) and gut lamina propria of VAD mice dependent on CCR7 signaling. Langerin(+) DCs have phenotypes more similar to those of bone marrow-derived dermal langerin(+) DCs than epidermal Langerhans cells. Moreover, RA receptor antagonists enhance the differentiation of langerin(+) DCs from mouse and human precursors of bone marrow and peripheral blood. Langerin(+) DCs were highly differentiated but less inflammatory than langerin(-) DCs of MLNs of VAD mice. Moreover, tolerance to orally delivered antigen was completely abrogated by depletion of langerin(+) DCs in the VAD mice. CONCLUSIONS: These results suggest that generation of langerin(+) DCs in the GALT is tightly regulated by RA and that the micro-environment of tissues determines the phenotype of DCs.
URI
http://hdl.handle.net/YU.REPOSITORY/22604http://dx.doi.org/10.1053/j.gastro.2009.11.006
ISSN
0016-5085
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약학대학 > 약학부 > Articles
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