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| Item Type: | Article |
|---|---|
| Title: | Lenalidomide regulates CNS autoimmunity by promoting M2 macrophages polarization |
| Creators Name: | Weng, Q., Wang, J., Wang, J., Wang, J., Sattar, F., Zhang, Z., Zheng, J., Xu, Z., Zhao, M., Liu, X., Yang, L., Hao, G., Fang, L., Lu, Q.R., Yang, B. and He, Q. |
| Abstract: | Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS. Depletion of macrophages by pharmacology treatment of clodronate liposomes or transferring lenalidomide-induced BMDMs in EAE mice completely abolished the therapeutic effect of lenalidomide or prevented EAE development, respectively. The macrophages-derived IL10 was upregulated both in vivo and in vitro after lenalidomide treatment. Moreover, lenalidomide-treated IL10-dificient EAE mice had higher clinical scores and more severe CNS damage, and intravenous injection of lenalidomide-treated IL10BMDMs into mice with EAE at disease onset did not reverse disease severity, implying IL10 may be essential in lenalidomide-ameliorated EAE. Mechanistically, lenalidomide significantly increased expression and autocrine secretion of IL10, subsequently activated STAT3-mediated expression of Ym1. These studies facilitate the development of potential novel therapeutic application of lenalidomide for the treatment of MS. |
| Keywords: | Autoimmunity, beta-N-Acetylhexosaminidases, Cell Count, Cell Differentiation, Central Nervous System, Clodronic Acid, Experimental Autoimmune Encephalomyelitis, Gene Expression Regulation, Immunologic Factors, Inbred C57BL Mice, Interleukin-10, Knockout Mice, Lectins, Lenalidomide, Liposomes, Macrophages, Microglia, Signal Transduction, STAT3 Transcription Factor, Th1 Cells, Animals, Mice |
| Source: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 2 |
| Page Range: | 251 |
| Date: | 14 February 2018 |
| Additional Information: | Erratum in: Cell Death & Dis 11:108 |
| Official Publication: | https://doi.org/10.1038/s41419-018-0290-x |
| PubMed: | View item in PubMed |
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