Liver Kinase B 1 Regulates Antigen Presentation Genes in Murine Astrocytes

Rylee N. Cisney*, Savannah G. Sims, Jacob Feldmann, and Gordon P. Meares

Microbiology, Immunology, and Cell Biology Department, School of Medicine, West Virginia University, Morgantown, WV 26506

Presentation Category: Oral-Science & Technology (Oral Presentation #25)

Student’s Major: Immunology and Medical Microbiology

Adaptive immunity is the body’s long-term memory immunity and is commonly found to be dysregulated in autoimmune diseases, such as Multiple Sclerosis (MS). Previous data has shown that a single nucleotide polymorphism (SNP) in the Liver Kinase B1 (LKB1) gene may be a risk factor for Multiple Sclerosis. LKB1 is a ubiquitous kinase protein involved in the regulation of metabolism, cell growth, and inflammatory activation. LKB1 is known to regulate cellular responses induced by the inflammatory cytokine interferon gamma (INF-γ). IFN-γ commonly induces the expression of major histocompatibility complex class I and II (MHC). MHCs are molecules that present processed antigen peptides to T cell receptors, causing the subsequent activation of the T cell. Activated T cells mount an adaptive immune response targeting the specific antigen and produce inflammatory cytokines, like IFN-γ. Our data show that gene expression of MHC class II and MHC class I is negatively regulated by LKB1 in response to IFN-γ in human astrocytoma cells. Now, we are interested to see how or if LKB1 regulates a number of antigen presentation genes in response to IFN-γ and IFN- α signaling in murine astrocytes. Preliminary data suggests that wildtype C57BL/6 murine astrocytes utilize LKB1 as a negative regulator of H2-Aa, H2-Ab1, H2-Eb1, H2-K1, CIITA, NLRC5, and STAT1 gene expression in response to IFN-γ and IFN-α signaling. Thus, identifying LKB1 as a potential checkpoint for adaptive immunity by constraining antigen presentation which there is an abundance of in autoimmune diseases, such as MS.

Funding: National Institutes of Health

Program/mechanism supporting research/creative efforts: Other, Paid Research Assistant funded by PI