UNRAVELLING THE ROLE OF MUCOSAL ASSOCIATED INVARIANT T CELLS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS AND ITS ANIMAL MODEL

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It’s considered a multifactorial disease, whose etiology involves both environmental and genetic factors. The innate and the adaptive immune systems have long been considered the main players in CNS inflammation, plaque formation and, ultimately, neurodegeneration. In the last 10 to 15 years a lot of attention has been focused on a newly described subset of immune cells, called unconventional T cells, as possible modulators of the aberrant activation of the immune system. The family of unconventional T cells comprises mucosal associated invariant T (MAIT),  and NKT cells. MAIT cells are innate-like T cells, recognizing riboflavin metabolites presented by the evolutionary conserved antigen presenting molecule MR1. They are abundant at mucosal sites and their phenotype is deeply influenced by the microbiome. They can be activated either by direct TCR stimulation or by cytokines produced during inflammation. Once activated, they can produce both pro-inflammatory cytokines and cytotoxic molecule, like granzyme B. MAIT cells have been implicated in the pathogenesis of many autoimmune diseases, such as diabetes, inflammatory bowel diseases and rheumatoid arthritis. In this project we aim to elucidate the potential role of MAIT cells in the pathogenesis of MS, by using both the animal model of the disease, experimental autoimmune encephalomyelitis (EAE) and samples obtained from people with MS (pwMS).