Multiple Sclerosis
- Multiple Sclerosis (MS) is the most common chronic inflammatory autoimmune disease of the Central Nervous System (CNS) and is the first cause of non-traumatic disability with prevalence in young adults, especially young women. Under inflammatory conditions, when blood brain barrier integrity is disrupted, monocytes enter the CNS parenchyma and can give rise to monocyte-derived macrophages (MoMF) . Monocyte and MoMF contributions to brain pathologies are well documented in MS and their involvement in the development, progression, and resolution of EAE (murine model of MS). In addition, during CNS inflammation, there is an increase in dendritic cells (DCs) recruitment and tissue infiltration. These cells are required for the activation of encephalitogenic T cells, resulting in the recruitment of other cells that contribute to CNS tissue damage. CD74 is expressed mostly in antigen-presenting cells (APCs), including macrophages and DCs. We previously characterized CD74 as a transcription regulator in healthy and CLL cells, forming complexes with various transcription factors that together regulate cell function. We suggest that CD74 functions in cell type-specific manner. Our hypothesis is in this project that CD74 acts as a transcription regulator in autoimmunity by playing a role in microglia, BAMs and/or DCs. CD74-ICD associates with different transcription factors in each cell type, resulting in regulation of wide variety of cellular processes and immune functions.
- Myeloid cells such as microglia and border associated macrophages are essential in the central nervous system. They participate in the process of neuroinflammation in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the murine model of Multiple Sclerosis (MS). The activation of those cells in EAE induces a cellular cascade that causes infiltration of immune cells that eventually damage the myelin coating of the neurons. SLAMF5 (CD84) was identified as a receptor that controls the disease severity in EAE model through the regulatory B population. In this project, we investigate the role of those cells in the disease progression through SLAMF5 expression. The SLAMF5 blocking antibody (B4) that was developed in our lab has strong potential as a target in autoimmune disorders such as Multiple Sclerosis.