Anthony Lyons,^1 *Eric J. Downer,^1 * Suzanne Crotty,³ Yvonne M. Nolan,³ Kingston H. G. Mills,² and Marina A. Lynch

Trinity College Institute for Neuroscience, Physiology Department, and ²Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland, and ³Biosciences Institute, University College, Cork, Ireland

Correspondence should be addressed to Prof. Marina A. Lynch, Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland. Email: lynchma@tcd.ie

Deficits in cognitive function are associated with neuroinflammatory changes, typified by activation of glial cells and an
alteration of the pro- and anti-inflammatory cytokine balance in the brain.  Although there is evidence to suggest that
activation of microglia is regulated by interaction with other cell types in the brain, the mechanism(s) involved is
poorly understood. Here, we provide evidence that interaction between CD200 and its receptor plays a role in
modulating microglial activation under conditions of  chronic and acute inflammation of the brain. We report that
 interleukin-4 (IL-4) plays a central role in modulating expression of CD200 and identify a mechanism by which
IL-4 directly controls microglial cell activation. Our findings provide the first demonstration of a role for IL-4 in
modulating CD200 expression and suggest a mechanism for regulation of microglial activation in the intact CNS
under inflammatory conditions.