Human CD1c⺠myeloid dendritic cells acquire a high level of retinoic acid-producing capacity in response to vitamin D3.
J Immunol
; 191(6): 3152-60, 2013 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-23966631
ABSTRACT
All-trans-retinoic acid (RA) plays a critical role in maintaining immune homeostasis. Mouse intestinal CD103⺠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⺠blood myeloid DCs (mDCs) but not CD141(high) 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. CD103â» rather than CD103⺠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. RALDH2(high) CD1c⺠mDCs stimulated naive CD4⺠T cells to express gut-homing molecules and to produce Th2 cytokines in an RA-dependent manner. This study suggests that CD1c⺠mDCs are a major human DC subset that produces RA in response to VD3 in the steady state. The "vitamin D-CD1câºmDC-RA" axis may constitute an important immune component for maintaining tissue homeostasis in humans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Células Dendríticas
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Glicoproteínas
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Colecalciferol
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Antígenos CD1
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Células Mieloides
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article