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Oxford University Press, International Immunology, 11(27), p. 589-596, 2015

DOI: 10.1093/intimm/dxv020

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Modulation of dendritic cell alternative activation and function by the vitamin A metabolite retinoic acid.

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract The archetypal T h 2 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 T h 2 polarization.