In:
The Journal of Immunology, The American Association of Immunologists, Vol. 191, No. 6 ( 2013-09-15), p. 3152-3160
Abstract:
All-trans-retinoic acid (RA) plays a critical role in maintaining immune homeostasis. Mouse intestinal CD103+ dendritic cells (DCs) produce a high level of RA by highly expressing retinal dehydrogenase (RALDH)2, an enzyme that converts retinal to RA, and induce gut-homing T cells. However, it has not been identified which subset of human DCs produce a high level of RA. In this study, we show that CD1c+ blood myeloid DCs (mDCs) but not CD141high mDCs or plasmacytoid DCs exhibited a high level of RALDH2 mRNA and aldehyde dehydrogenase (ALDH) activity in an RA- and p38-dependent manner when stimulated with 1α,25-dihydroxyvitamin D3 (VD3) in the presence of GM-CSF. The ALDH activity was abrogated by TLR ligands or TNF. CD103− rather than CD103+ human mesenteric lymph node mDCs gained ALDH activity in response to VD3. Furthermore, unlike in humans, mouse conventional DCs in the spleen and mesenteric lymph nodes gained ALDH activity in response to GM-CSF alone. RALDH2high CD1c+ mDCs stimulated naive CD4+ T cells to express gut-homing molecules and to produce Th2 cytokines in an RA-dependent manner. This study suggests that CD1c+ mDCs are a major human DC subset that produces RA in response to VD3 in the steady state. The “vitamin D – CD1c+ mDC – RA” axis may constitute an important immune component for maintaining tissue homeostasis in humans.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1203517
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
