The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets.

ABSTRACT: TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells, switched memory B cells, and IFNAR signaling were decreased in healthy individuals that expressed the protective variant TYK2^A1104 (TYK2^P ). To study this variant in vivo, we developed a knock-in murine model of this allele. Murine T

SUBMITTER: Gorman JA 

PROVIDER: S-EPMC6355696 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature