Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues

SY Chang, HR Cha, JH Chang, HJ Ko, H Yang… - Gastroenterology, 2010 - Elsevier
SY Chang, HR Cha, JH Chang, HJ Ko, H Yang, B Malissen, M Iwata, MN Kweon
Gastroenterology, 2010Elsevier
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 (TH17) 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 …
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 (TH17) 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 microenvironment of tissues determines the phenotype of DCs.
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