Loading...
Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity
Sherman, Linda A
Sherman, Linda A
Abstract
The 1858C>T allele of the tyrosine phosphatase PTPN22 is present in 5-10% of the North American population and is strongly associated with numerous autoimmune diseases. Although research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its pro-autoimmune allele has in anti-viral immunity remains poorly defined. Here, we use single cell RNA-sequencing and functional studies to interrogate the impact of this pro-autoimmune allele on anti-viral immunity during Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13) infection. Mice homozygous for this allele (PEP-619WW) clear the LCMV-cl13 virus whereas wildtype (PEP-WT) mice cannot. This is associated with enhanced anti-viral CD4 T cell responses and a more immunostimulatory CD8α- cDC phenotype. Adoptive transfer studies demonstrated that PEP-619WW enhanced anti-viral CD4 T cell function through virus-specific CD4 T cell intrinsic and extrinsic mechanisms. Taken together, our data show that the pro-autoimmune allele of Ptpn22 drives a beneficial anti-viral immune response thereby preventing what is normally a chronic virus infection.
Description
Date
2024-03-21
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS One
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
Citation
Orozco RC, Marquardt K, Pratumchai I, Shaikh AF, Mowen K, Domissy A, Teijaro JR, Sherman LA. Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity. PLoS Pathog. 2024 Mar 21;20(3):e1012095. doi: 10.1371/journal.ppat.1012095. PMID: 38512979; PMCID: PMC10987006