Cell-type-specific requirement for TYK2 in murine immune cells under steady state and challenged conditions.

ABSTRACT: Tyrosine kinase 2 (TYK2) deficiency and loss or inhibition of kinase activity in men and mice leads to similar immune compromised phenotypes, predominantly through impairment of interferon (IFN) and interleukin 12 family responses. Here we relate the transcriptome changes to phenotypical changes observed in TYK2-deficient (Tyk2^-/-) and TYK2 kinase-inactive (Tyk2^K923E) mice in naïve splenic immune cells and upon ex vivo IFN treatment or in vivo tumor transplant infiltration. The TYK2 activities under homeostatic and both challenged conditions are highly cell-type-specific with respect to quantity and quality of transcriptionally dependent genes. The major impact of loss of TYK2 protein or kinase activity in splenic homeostatic macrophages, NK and CD8⁺ T cell

SUBMITTER: Karjalainen A 

PROVIDER: S-EPMC11872851 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature