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

作者：Chang Sun Young; Cha Hye Ran; Chang Jae Hoon; Ko Hyun Jeong; Yang Hyungjun; Malissen Bernard; Iwata Makoto; Kweon Mi Na^*

来源：Gastroenterology, 2010, 138(4): 1468-U332.

DOI：10.1053/j.gastro.2009.11.006

• Dendritic Cells
• Langerin
• Retinoic Acid
• Gut

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.

• 出版日期2010-4