Project R-11247

Neutrophils: underestimated players in the pathogenesis of multiple sclerosis (MS) (Research)

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, of which the etiologic basis remains elusive and for which no curing treatment is available. It is currently believed to be mostly driven by the adaptive immune cells, more specifically, myelin-specific, autoreactive T cells. These T cells penetrate into the central nervous system, over an inflamed blood brain barrier (BBB) to initiate an inflammatory cascade that results in the influx of other immune cells, concomitantly with the production of chemokines, cytokines and other immunomodulatory molecules. Recently, interest developed in the role of neutrophils in the pathogenesis of MS, supported by evidence from mouse models of the disease and studies on patient samples. However, it is unclear how neutrophils would contribute to the pathology. I aim to phenotypically characterize neutrophils from MS patients and discover distinct subsets, potentially related to different treatments. In addition, I will assess the mechanisms by which neutrophils influence disease pathogenesis by exploring 3 effector functions of neutrophils related to MS; phagocytosis of myelin, breakdown of the BBB and antigen presentation. Also, I want to investigate the effect of MS-approved drugs on the function and phenotype of neutrophils. The last step of this project is to verify the obtained results in vivo using intravital imaging in the cuprizone mouse model for MS.

01 November 2020 - 31 October 2022