Lenalidomide regulates CNS autoimmunity by promoting M2 macrophages polarization

• DOI: 10.1038/s41419-018-0290-x
• Publication Date: 2018-02-14T15:02:19Z
• Authors: Qinjie Weng; Jiaying Wang; Jiajia Wang; Jing Wang; Fahmida Sattar; Zhikang Zhang; Jiahuan Zheng; Zijie Xu; Mengting Zhao; Xuan Liu; Lijun Yang; Guifeng Hao; Liang Fang; Q. Richard Lu; Bo Yang; Qiaojun He
• Keywords: Central Nervous System; STAT3 Transcription Factor; 0301 basic medicine; Cancer Research; Encephalomyelitis, Autoimmune, Experimental; Autoimmunity; Cell Count; Article; Mice; 03 medical and health sciences; Lectins; Animals; Immunologic Factors; Lenalidomide; Mice, Knockout; Macrophages; Cell Differentiation; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Gene Expression Regulation; Liposomes; Female; Microglia; Clodronic Acid

Abstract Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration leukocytes into CNS subsequent demyelination. Emerging evidences have revealed beneficial roles M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), model for MS. Here, we identify that lenalidomide alone could promote polarization to prevent progression EAE, which associated with inhibition proinflammatory Th1 Th17 cells both peripheral lymph CNS. Depletion pharmacology treatment clodronate liposomes or transferring lenalidomide-induced BMDMs EAE mice completely abolished therapeutic effect prevented development, respectively. The macrophages-derived IL10 was upregulated vivo vitro after treatment. Moreover, lenalidomide-treated IL10-dificient had higher clinical scores more severe damage, intravenous injection −/− at disease onset did not reverse severity, implying may be essential lenalidomide-ameliorated EAE. Mechanistically, significantly increased expression autocrine secretion IL10, subsequently activated STAT3-mediated Ym1. These studies facilitate development potential novel application