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.
Elucidating the role of the Blood-Brain Barrier
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.