Production of CCL2 by CNS resident cells regulates development of EAE through the recruitment of TNF-α and iNOS expressing macrophages (129.19)

Abstract Experimental autoimmune encephalomyelitis (EAE) is demyelinating disease of the central nervous system (CNS), which serves as an animal model for Multiple Sclerosis (MS). Increased expression of CCL2, monocyte chemoattractant protein-1 has been detected in CNS inflammatory infiltrates, which consist of T cells, macrophages, and B cells. The critical role for CCL2 in MS-like diseases was identified in mice that lack this molecule and develop less severe EAE and impaired macrophages recruitment into the CNS. While CCL2 production is essential for macrophage infiltration into the CNS, it remains unclear which cell source is critical in disease induction. We constructed radiation bone marrow chimera to investigate the cell-specific source of CCL2 production in EAE. Mice lacking CCL2 production by resident CNS cells showed a delayed and diminished clinical disease as result of decreased macrophage infiltration into the CNS. Moreover, TNF-α and iNOS producing TipDC recruitment to CNS was reduced in mice devoid of CCL2 production by CNS resident cells. Mice lacking CCL2 production by infiltrating mononuclear cells developed EAE similar to controls. Our study demonstrates that CCL2 production by CNS resident cells is the major contributors to trafficking of macrophages into the CNS and subsequent disease progressions. Supported by NIH NS034510