Final published version
Licence: CC BY
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Modulation of dendritic cell alternative activation and function by the vitamin A metabolite retinoic acid
AU - Jones, Lucy H
AU - Cook, Peter C
AU - Ivens, Alasdair C
AU - Thomas, Graham D
AU - Phythian-Adams, Alexander T
AU - Allen, Judith E
AU - MacDonald, Andrew S
N1 - © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society for Immunology.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - The archetypal Th2 cytokine IL-4 has previously been shown to alternatively activate murine macrophages and, more recently, dendritic cells (DCs) both in vitro and in vivo. IL-4 has also been shown to induce Aldh1a2 (aldehyde dehydrogenase 1a2) expression in murine macrophages recruited to the peritoneal cavity. However, the influence of IL-4 on DC Aldh1a2 induction in vivo has not yet been addressed. In this work, we found that DCs show enhanced aldehyde dehydrogenase enzyme activity in vivo, which led us to investigate the impact of the vitamin A metabolite all-trans retinoic acid (RA) on DC alternative activation and function. Antagonism of RA receptors reduced production of resistin-like molecule alpha by DCs responding to IL-4, while addition of exogenous RA enhanced production of this marker of alternative activation. Functionally, RA increased DC induction of CD4(+) T-cell IL-10, while reducing CD4(+) T-cell IL-4 and IL-13, revealing a previously unidentified role for RA in regulating the ability of alternatively activated DCs to influence Th2 polarization.
AB - The archetypal Th2 cytokine IL-4 has previously been shown to alternatively activate murine macrophages and, more recently, dendritic cells (DCs) both in vitro and in vivo. IL-4 has also been shown to induce Aldh1a2 (aldehyde dehydrogenase 1a2) expression in murine macrophages recruited to the peritoneal cavity. However, the influence of IL-4 on DC Aldh1a2 induction in vivo has not yet been addressed. In this work, we found that DCs show enhanced aldehyde dehydrogenase enzyme activity in vivo, which led us to investigate the impact of the vitamin A metabolite all-trans retinoic acid (RA) on DC alternative activation and function. Antagonism of RA receptors reduced production of resistin-like molecule alpha by DCs responding to IL-4, while addition of exogenous RA enhanced production of this marker of alternative activation. Functionally, RA increased DC induction of CD4(+) T-cell IL-10, while reducing CD4(+) T-cell IL-4 and IL-13, revealing a previously unidentified role for RA in regulating the ability of alternatively activated DCs to influence Th2 polarization.
KW - Aldehyde Dehydrogenase
KW - Animals
KW - Antigens, Surface
KW - Dendritic Cells
KW - Enzyme Activation
KW - Female
KW - Immunomodulation
KW - Immunophenotyping
KW - Intercellular Signaling Peptides and Proteins
KW - Interleukin-4
KW - Mice
KW - Phenotype
KW - Receptors, Retinoic Acid
KW - Signal Transduction
KW - T-Lymphocytes
KW - Tretinoin
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/intimm/dxv020
DO - 10.1093/intimm/dxv020
M3 - Journal article
C2 - 25899567
VL - 27
SP - 589
EP - 596
JO - International Immunology
JF - International Immunology
SN - 1460-2377
IS - 11
ER -