Saturday, November 23, 2024
11/23/2024
PROJECT SUMMARY/ABSTRACT Multiple sclerosis (MS) is considered to be a T cell-mediated autoimmune disease, and the relationship between initial innate immune activity and neurodegeneration is still poorly understood. In this proposed project, we aim to elucidate how the novel protective role of dectin-1, a C-type lectin receptor (CLR), is exerted through crosstalk of myeloid cells infiltrated in the central nervous system (CNS) and CNS-resident cells in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination (CID) models. Dectin-1 has been one of the most intensively studied innate immune receptors, detecting fungal cell wall to induce inflammation. However, we recently found that dectin-1 is a protective molecule in EAE, and the protective role of dectin-1 in neuroinflammation has not been defined. In particular, the role of dectin-1 in MS/EAE is entirely unknown. Our preliminary data also strongly suggested that endogenous molecules, expressed at least on astrocytes, trigger the protective role of dectin-1. The goal of this project is to delineate how innate immune activities lead to neuroprotection in EAE. Based on our preliminary data, our central hypothesis is: Myeloid cells sense endogenous inflammatory cues through dectin-1 to mediate crosstalk between the immune system and CNS that promotes neuroprotection. This study will contribute to a growing body of evidence that dectin-1 has importance beyond the context of fungal infection. We advance this emerging understanding by identifying a new protective mechanism of Dectin-1, specifically in the setting of CNS autoimmunity and neurodegeneration. This project will provoke consideration of dectin-1 and its effector functions beyond the context of infection to provide potential novel targets for therapeutic intervention in neuroinflammatory disorders.
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