Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity

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 have 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
CD8a- 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.