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


METHODS
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.
Chang
Sun-Young
SY
Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
Cha
Hye-Ran
HR
Chang
Jae-Hoon
JH
Ko
Hyun-Jeong
HJ
Yang
Hyungjun
H
Malissen
Bernard
B
Iwata
Makoto
M
Kweon
Mi-Na
MN
D000445:Aldehyde Oxidoreductases / Q000502:physiology; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D007108:Immune Tolerance; D007422:Intestines / Q000276:immunology*; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D037181:Lectins, C-Type / Q000502:physiology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000502:physiology; D014212:Tretinoin / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000276:immunology
D000954:Antigens, Surface; C515371:Ccr7 protein, mouse; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D054400:Receptors, CCR7; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse