CCR4 contributes to the pathogenesis of experimental autoimmune encephalomyelitis by regulating inflammatory macrophage function

Chemokines and their receptors play a critical role in orchestrating the immune response during experimental autoimmune encephalomyelitis (EAE). Expression of CCR4 and its ligand CCL22 has been observed in ongoing disease. Here we describe a role for CCR4 in EAE, illustrating delayed and decreased disease incidence in CCR4(-/-) mice corresponding with diminished CNS infiltrate. Peripheral T cell responses were unaltered in CCR4(-/-) mice; rather, disease reduction was related to reduced CD11b(+)Ly6C(hi) inflammatory macrophage (iW phi) numbers and function. These results provide evidence that CCR4 regulates EAE development and further supports the involvement of CCR4 in iM phi effector function. (C) 2011 Elsevier B.V. All rights reserved.