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

• Published in: Journal of neuroimmunology 2011-07, Vol.236 (1), p.17-26
• Main Authors: Forde, Eileen A, Dogan, Rukiye-Nazan E, Karpus, William J
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Amino Acid Sequence; Animals; CCR4; Central nervous system; Chemokine receptor; Encephalomyelitis, Autoimmune, Experimental - etiology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental autoimmune encephalomyelitis; Female; Inflammation Mediators - physiology; Inflammatory macrophage; Macrophages - metabolism; Macrophages - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Multiple sclerosis; Neurology; Receptors, CCR4 - physiology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2011.04.008

Abstract 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+ Ly6Chi inflammatory macrophage (iMϕ) numbers and function. These results provide evidence that CCR4 regulates EAE development and further supports the involvement of CCR4 in iMϕ effector function.