Alec Bevis

The PTPN22 common minor allelic variant, rs2476601, is present in 5-15% of North Americans and is associated with multiple autoimmune diseases. PTPN22 is expressed exclusively in immune cells and regulates numerous immune cell functions including T-cell receptor (TCR) signaling and the selective production of type I interferons.  Previous studies show that mice lacking Ptpn22 (PEP-null) or expressing the murine equivalent of the minor allele (PEP-619WW) can clear the chronic virus infection Lymphocytic choriomeningitis virus clone 13 (LCMV-cl13) where wildtype (PEP-WT) mice cannot. This is paired with enhanced T cell and myeloid cell function over PEP-WT animals. However, the mechanisms by which PEP-null and PEP-619WW mice clear chronic virus infection are poorly understood. Additionally, the cell-autonomous role of Ptpn22 in myeloid cells during virus infection remains unclear. This research aims to interrogate the cell-specific effects accountable for this increased LCMV-cl13 clearance and how the loss of Ptpn22 or its minor allelic variant impacts other virus infections, and how commercially available Ptpn22 inhibitors may be therapeutically exploited through chemical and biological inhibition to enhance viral clearance. Considering PTPN22regulates a wide range of immune functions, it is vital to better understand the pivotal role this gene may play in the balance between sufficient anti-viral immune responses and overactive responses leading to autoimmunity.