The expression and function of IL-33 within the CNS and during the pathogenesis of Multiple Sclerosis

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2015
Thesis identifier
  • T13984
Qualification Level
Qualification Name
Department, School or Faculty
  • Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) effecting millions of people worldwide. The pathology of MS is characterised by the demyelination of neurons. Though the root cause of MS remains elusive a combination of genetic, environmental and infectious factors are thought to contribute. IL-33 has previously been shown to be protective (e.g. atherosclerosis), or detrimental (e.g. asthma), in certain disease states. IL-33 and ST2 (IL-33R) are highly expressed within the CNS and have been shown to exacerbate Experimental Autoimmune Encephalomyelitis (mouse model of Multiple Sclerosis). In-situ staining was used to indicate expression of IL-33 and ST2 in the CNS at different stages of EAE disease. IL-33 remained unchanged throughout the time course of disease. However, ST2 expression was upregulated during cellular infiltration. Within naìˆve and EAE mice IL-33 and ST2 were both expressed on astrocytes and neurons. In acute and chronic MS tissues IL-33 was highly expressed by neurons and axons. Within the lesions IL-33 was present on damaged axons as well as microglia and ODCs. ST2 displayed a diffuse staining in control and MS tissues, however within the lesion site of acute and chronic MS samples ST2 surrounded damaged axons and was present on several ODCs. The potential for IL-33 to affect myelination was investigated using an in-vitro culture system. IL-33 significantly reduced myelination within rat cultures, however no significant effect was observed within the mouse culture system. The main findings from EAE tissues were corroborated in human MS tissue and the implications this may have on understanding the disease course of MS are discussed.
Resource Type
Date Created
  • 2015
Former identifier
  • 1218967