Accuri C6 Flow Cytometer System
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Published online before print May 19, 2009
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1008600

Received for publication October 6, 2008.
Revised March 30, 2009.
Accepted for publication March 31, 2009.

Article

Liver X receptor agonist regulation of Th17 lymphocyte function in autoimmunity

Jihong Xu , Gail Wagoner , James C. Douglas , and Paul D. Drew @

Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

@ To whom correspondence should be addressed. E-mail: drewpauld{at}uams.edu.


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Abstract

CD4+ Th17 cells are believed to play an important role in the development of a variety of autoimmune diseases including EAE, an animal model of MS. Previously, we and others demonstrated that LXR agonists suppressed the activation of primary glial cells and blocked the development of EAE. The present studies demonstrated that the LXR agonist T0901317 suppressed IL-17A expression from splenocytes derived from V{alpha}2.3/V{beta}8.2 TCR transgenic mice and from MOG35–55-immunized C57BL/6 mice. Furthermore, in vitro treatment with IL-23 alone or in combination with MOG35–55 induced IL-17A expression from splenocytes derived from MOG35–55-immunized mice, and T0901317 blocked this induction. In vitro treatment with the LXR agonist suppressed IL-23R expression by splenocytes. In addition, in vivo treatment with the LXR agonist suppressed IL-17A and IL-23R mRNA and protein expression in EAE mice. These studies suggest that LXR agonists suppress EAE, at least in part by suppressing IL-23 signaling. Recent studies indicate that the cytokines IL-21 and IL-22 are produced by Th17 cells and modulate immune responses. Our studies demonstrate that the LXR agonist T0901317 suppressed MOG35–55-induced expression of IL-21 and IL-22 mRNA in splenocytes derived from MOG35–55-immunized mice. Finally, we demonstrate that the LXR agonist T0901317 suppressed the development of EAE in an experimental paradigm involving treatment of established EAE. Collectively, these studies suggest that LXR agonists may be effective in the treatment of MS.

Key Words: cytokines • EAE/MS




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