Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system.

Susan C. Barnett,Christopher Linnington,Cornelia Schuh,Hans Lassmann,Karen J. Fairlie-Clarke,Hui-Rong Jiang,Debbie Allan,Christina Elliott

doi:10.1186/s40478-016-0344-1

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0344-1) contains supplementary material, which is available to authorized users.

Highlights

Signal transduction by Interleukin-33 (IL-33) is implicated in the pathogenesis of an increasing number of human diseases [1,2,3], in which it is generally regarded to act as an alarmin that alerts the immune system to necrotic cell injury and tissue damage [4,5,6]
Altered expression level and pattern of IL-33 in lesions of multiple sclerosis (MS) patient brain tissues To determine the expression of IL-33 in MS lesions, immunohistochemical staining was performed in human brain tissues from all MS patients and controls as described in Materials and Methods
Expression of IL-33 in the cortex and normal appearing white matter (WM) (NAWM) from chronic MS patients was similar to tissues of controls (Fig. 1c, f )

Summary

Introduction

Signal transduction by Interleukin-33 (IL-33) is implicated in the pathogenesis of an increasing number of human diseases [1,2,3], in which it is generally regarded to act as an alarmin that alerts the immune system to necrotic cell injury and tissue damage [4,5,6]. The role of IL-33 in inflammatory CNS diseases such as multiple sclerosis (MS) is of particular interest as MS is a disease characterised by immune-mediated demyelination of axons, IL-33 has the potential to modulate both the immune and the CNS system and to influence disease pathology This is supported by recent findings of increased expression of IL-33 in the

Methods

Results

Discussion

Conclusion