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 -