title: Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system.
abstract: Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer's disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Allan
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Fairlie-Clarke
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Elliott
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schuh
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland, UK.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Barnett
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University Vienna, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Linnington
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, UK. huirong.jiang@strath.ac.uk.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jiang
mesh_terms: D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism*; D000067596:Interleukin-33 / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D017472:Receptors, Interleukin-1; C000589812:ST2 protein, rat
keywords: IL-33; Multiple sclerosis; Myelination; Oligodendrocyte; ST2