Repeated 0.5-Gy gamma irradiation attenuates experimental autoimmune encephalomyelitis with up-regulation of regulatory T cells and suppression of IL17 production.
We recently reported attenuation of autoimmune disease by low-dose gamma irradiation (repeated doses of 0.5 Gy) in MRL-lpr/ lpr mice. Here we studied the effect of low-dose gamma irradiation on experimental autoimmune encephalomyelitis (EAE), which is a rodent model of multiple sclerosis. SJL/J mice were immunized with myelin basic protein for the induction of EAE and were exposed to 0.5 Gy gamma rays once a week for 4 weeks. Radiation suppressed incidence and disease severity scores and delayed the onset of pathological changes. Pro-inflammatory cytokines (IFN-gamma and IL6), autoantibody and CD8+ cytotoxic T cells are involved in the appearance of EAE. Radiation suppressed the increases in these cytokines and the autoantibody production and blocked the increase in the population of CD8+ cytotoxic T cells. Production of IL17 by Th17 cells and/or gammadelta T cells, which plays a crucial role in EAE, was also significantly suppressed by radiation. Furthermore, a significant increase in regulatory T cells, which are involved in suppression of autoimmune disease, was found in irradiated EAE mice. These data suggest that low-dose gamma irradiation attenuates EAE through suppression of pro-inflammatory cytokines, reduction of cytotoxic T cells and induction of regulatory T cells.
Tsukimoto
Mitsutoshi
M
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. tsukim@rs.noda.tus.ac.jp
Nakatsukasa
Hiroko
H
Sugawara
Keigo
K
Yamashita
Keiichiro
K
Kojima
Shuji
S
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D007114:Immunization; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D015854:Up-Regulation
D015703:Antigens, CD; D020381:Interleukin-17; D004676:Myelin Basic Protein