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Role of sexual dimorphisms in blood-brain barrier permeability on central nervous system autoimmunity.
One of the puzzling questions with autoimmunity overall and multiple sclerosis (MS) in particular is its sexual bias. Women are consistently more affected than men in myriad autoimmune disorders like rheumatoid arthritis (RA), systemic lupus erythematous (SLE), Graves’ disease, and MS among others. Fortunately, scientists are able to recapitulate some aspects of sex-related autoimmunity using murine systems. Female SJL mice are highly susceptible to experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Moreover, they also exhibit a relapsing-remitting (RR) disease pattern. Noteworthy 80% of MS patients are women diagnosed with RRMS; therefore the SJL-EAE is a very useful tool to recapitulate central nervous system (CNS) autoimmunity. Female SJL are also vulnerable to SLE and RA, sexually biases autoimmune disorders that could affect the nervous system, directly or indirectly. My career goal is to elucidate the mechanisms underlying the neuropathophysiology surrounding sex-related autoimmune disorders, addressing the sexual dimorphisms at the interphase of neuro-immune systems and their role in female susceptibility to autoimmunity. Specifically, my research focuses on sexual dimorphism of the blood-brain barrier (BBB) microvasculature as a relevant contributor to MS neuropathogenesis with the purpose of developing sex-specific therapeutic targets. Towards this goal, I dedicated my postdoctoral training first, to uncovering the molecular mechanism underlying changes in apicobasal polarity of the chemokine CXCL12 at the BBB, a key regulator of immune trafficking into the CNS, followed by studies determining how BBB polarity is differentially regulated in females during CNS autoimmunity.