Abstract Details

Title The Role of Cyclophilin A in Immune-mediated CNS Inflammation

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-058

Objective Cyclophilin A, also known as peptidylprolyl isomerase A, is an 18 kDa protein that has known function in immunity and inflammation, but the specific contribution of cyclophilin A to CNS inflammation remains to be clarified. The objective is to define the contribution of cyclophilin A to immune-mediated CNS inflammation.

Background Intracellular cyclophilin A is known to modulate T cell receptor signaling. Extracellular (secreted) cyclophilin A can function as a leucocyte chemotactic factor during inflammation. We previously showed that NIM811, a non-selective cyclophilin inhibitor ameliorated experimental allergic encephalomyelitis (EAE), a model of immune-mediated CNS inflammation, by a mechanism independent of its action on cyclophilin D and calcineurin, suggesting a cyclophilin A-dependent mechanism (Huang, Z et al. J Immunol. 2017).

Design/Methods To study the role of cyclophilin A in CNS inflammation, we compared the neuroimmunology of EAE in cyclophilin A knockout (KO) mice and wild type littermates by fluorescence assisted cell sorting (FACS) analysis, immunohistochemical analysis and ex vivo antigen-recall response.

Results Cyclophilin A KO mice tended to have lower incidence of EAE following active induction (78% vs. 97%, p = 0.07, Fisher’s exact test). Cyclophilin A KO mice undergoing EAE showed significantly less infiltration of CD3+ T cells compared to wild type littermates (p = 0.0047) based on FACS analysis. Decrease in CD3+ T cell infiltration was confirmed by immunohistochemical analysis. Immune activation was altered in cyclophilin A KO mice compared to wild type litteramates as evidenced by reduced interferon-gamma production by cyclophilin A KO splenocytes in response to ex vivo myelin oligodendrocyte glycoprotein (MOG) stimulation (p = 0.021).

Conclusions The data suggest that cyclophilin A may contribute to peripheral immune activation and leucocyte infiltration during CNS inflammation.

Authors/Disclosures
Unsong Oh, MD (Virginia Commonwealth University School of Medicine) PRESENTER	Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��