Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid

Ting Feng, Yingzi Cong, Hongwei Qin, Etty N. Benveniste, Charles O. Elson

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.

Original languageEnglish (US)
Pages (from-to)5915-5925
Number of pages11
JournalJournal of Immunology
Volume185
Issue number10
DOIs
StatePublished - Nov 15 2010
Externally publishedYes

Fingerprint

Tretinoin
Dendritic Cells
Bone Marrow
Regulatory T-Lymphocytes
varespladib methyl
Vitamin A
Inbred C57BL Mouse
Bone Marrow Cells
Immunoglobulin A
Homeostasis
B-Lymphocytes
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. / Feng, Ting; Cong, Yingzi; Qin, Hongwei; Benveniste, Etty N.; Elson, Charles O.

In: Journal of Immunology, Vol. 185, No. 10, 15.11.2010, p. 5915-5925.

Research output: Contribution to journalArticle

Feng, Ting ; Cong, Yingzi ; Qin, Hongwei ; Benveniste, Etty N. ; Elson, Charles O. / Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. In: Journal of Immunology. 2010 ; Vol. 185, No. 10. pp. 5915-5925.
@article{1877d8ef91f341a6ad87161dc2b7eb96,
title = "Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid",
abstract = "It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.",
author = "Ting Feng and Yingzi Cong and Hongwei Qin and Benveniste, {Etty N.} and Elson, {Charles O.}",
year = "2010",
month = "11",
day = "15",
doi = "10.4049/jimmunol.1001233",
language = "English (US)",
volume = "185",
pages = "5915--5925",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid

AU - Feng, Ting

AU - Cong, Yingzi

AU - Qin, Hongwei

AU - Benveniste, Etty N.

AU - Elson, Charles O.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.

AB - It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by inhibiting suppressor of cytokine signaling 3 expression and thereby enhancing STAT3 activation. These RA effects were evident in vivo, in that mucosal DCs from vitamin A-deficient mice had reduced mucosal DC function, namely failure to induce Foxp3+ regulatory T cells. Furthermore, MyD88 signaling enhanced RA-educated DC ALDH1a2 expression and was required for optimal TGF-β production. These data indicate that RA plays a critical role in the generation of mucosal DCs from bone marrow and in their functional activity.

UR - http://www.scopus.com/inward/record.url?scp=78650645161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650645161&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1001233

DO - 10.4049/jimmunol.1001233

M3 - Article

VL - 185

SP - 5915

EP - 5925

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -