TRAF3 enhances type I interferon receptor signaling in T cells by modulating the phosphatase PTPN22

Type I interferons (IFNs) are among the most powerful tools that host cells deploy against intracellular pathogens. Their effectiveness is due both to the rapid, directly antiviral effects of IFN-stimulated gene products and to the effects of type I IFN on responding immune cells. Type I IFN signaling through its receptor, IFNAR, is tightly regu-lated at multiple steps in the signaling cascade, including at the level of IFNAR downstream effectors, which in-clude the kinase JAK1 and the transcriptional regulator STAT1. Here, we found that tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) enhanced the activation of JAK1 and STAT1 specifically in CD4(+) T cells by preventing recruitment of the negative regulatory phosphatase PTPN22 to the IFNAR complex. The balance between signals through IFNAR and other cytokine receptors influences CD4(+) T cell differentiation and function during infections. Our work reveals TRAF3 and PTPN22 as key regulators of CD4(+) T cell activation by type I IFNs.

Automated summary

Type I interferons (IFNs) are powerful tools used by host cells to fight against intracellular pathogens. This study reveals the role of tumor necrosis factor receptor-associated factor 3 (TRAF3) and phosphatase PTPN22 in regulating CD4(+) T cell activation by type I IFNs. The balance between signals from IFNAR and other cytokine receptors influences CD4(+) T cell differentiation and function during infections.