title: Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice.
abstract: Interleukin-33 (IL-33) is usually expressed in the nucleus as a non-histone chromatin-associated protein. After passively released by necrotic cells, it functions as an IL-1 family member. IL-33 is highly expressed in the central nervous system (CNS), whether IL-33 is actively released in the CNS and involved in experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we found that IL-33 and receptor ST2 were expressed in the spinal cord of naïve mice. Compared to naive situation, the intracellular IL-33 was dramatically decreased and extracellular IL-33 was markedly increased in the spinal cord in the pre-onset, onset and peak stage of EAE. In the chronic stage, the reverse happened. The decrease of intracellular IL-33 was related to the activation of astrocytes and the damage of neurons in situ during EAE. Astrocytes secreted IL-33 actively upon inflammatory stimulation in vitro. Furthermore, blockage of the CNS-derived IL-33 exacerbated EAE development. Our data demonstrated that IL-33 was released by activated astrocytes actively, and by damaged neurons during EAE. It plays a suppressive role in EAE development via an autocrine or paracrine manner. Our findings are helpful to understand the release feature and function of the CNS-derived IL-33 and supply a potential therapeutic target for multiple sclerosis.
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: L
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: B
authors.initials: B
authors.lastname: Ming
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: M
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: H
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: P
authors.initials: P
authors.lastname: Xiong
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: F
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhengfangtj@hust.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018123:Receptors, Interleukin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D018123:Receptors, Interleukin
keywords: astrocyte; central nervous system; experimental autoimmune encephalomyelitis; interleukin-33; neuron