Mechanism of experimental autoimmune encephalomyelitis in Lewis rats: recent insights from macrophages

Abstract

Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is an acute monophasic paralytic central nervous system disease, in which most rats spontaneously recover from paralysis. EAE in Lewis rats is induced by encephalitogenic antigens, including myelin basic protein. EAE is mediated by CD4(+) Th1 cells, which secrete pro-inflammatory mediators, and spontaneous recovery is mediated by regulatory T cells. Recently, it was established that classically activated macrophages (M1 phenotype) play an important role in the initiation of EAE, while alternatively activated macrophages (M2 phenotype) contribute to spontaneous recovery from rat EAE. This review will summarize the neuroimmunological aspects of active monophasic EAE, which manifests as neuroinflammation followed by neuroimmunomodulation and/or neuroprotection, with a focus on the role of alternatively activated macrophages.

Keywords: Experimental autoimmune encephalomyelitis; Lewis rats; Macrophages; Neuroimmunomodulation; Regulatory T lymphocytes.

Fig. 1

Schematic diagram of the putative role of each macrophage phenotype in active monophasic experimental autoimmune encephalomyelitis (EAE) in Lewis rats. EAE is mediated by CD4⁺ Th1 cells and is further accelerated by classically activated macrophages (M1), while spontaneous recovery from rat EAE is associated with regulatory T cells and alternatively activated macrophages (M2). IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; TGF, transforming growth factor; TNF, tumor necrosis factor.

Fig. 2

Schematic diagram of the relationship between clinical signs and inflammatory cells and their products in active monophasic experimental autoimmune encephalomyelitis. Clinical signs largely match the patterns of inflammatory molecules. iNOS, inducible nitric oxide synthase; NK, natural killer; T-reg, regulatory T cell.