Poster abstracts
Poster number 60 submitted by Cora L. Petersen
Role of Autotaxin in Central Nervous System Autoimmunity
Cora L. Petersen (Neuroscience Graduate Program ), Yue Liu (Department of Microbial Infection and Immunity, The Ohio State University), Shawn Murphy (Department of Microbial Infection and Immunity, The Ohio State University), Joshua Deffenbaugh (Department of Microbial Infection and Immunity, The Ohio State University), Amy Lovett-Racke (Department of Microbial Infection and Immunity, The Ohio State University)
Abstract:
Background:
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS). A defining characteristic of MS is the ability of autoreactive T lymphocytes to cross the blood brain barrier (BBB) and mediate inflammation within the CNS. Previous study from our lab has found the gene ENPP2 to be highly upregulated in encephalitogenic T cells in the mouse model of MS. ENPP2 codes for the secreted protein autotaxin which promotes transendothelial migration of T cells from the blood stream into the lymphatic system. Our hypothesis is that inhibiting autotaxin signaling may prevent autoreactive T cells from crossing the BBB and causing neuroinflammation.
Aims:
Aim 1: Do MS patient CD4+ T cells show differential expression of autotaxin compared to healthy controls?
Aim 2: Does pharmacological inhibition of autotaxin ameliorate the mouse model of MS, experimental autoimmune encephalomyelitis (EAE)?
Method:
Peripheral blood mononuclear cells from MS patients and healthy controls were activated and analyzed for changes in autotaxin expression via flow cytometry. For EAE studies, mice were immunized to induce EAE and then treated with autotaxin inhibitor HA-130. Changes to disease severity were measured by tracking clinical score.
Results/Conclusions:
Our data show that MS patients’ CD4+ T cells differentially express autotaxin compared to healthy controls. In the context of EAE, we have found that treatment with autotaxin inhibitor HA-130 decreases EAE severity but does not affect the ability of CD4+ T cells to clear viral infection, suggesting autotaxin inhibition may be a viable therapeutic target.
Keywords: Neuroimmunology, Autoimmunity, Multiple Sclerosis