Myeloid Cell-Intrinsic IRF5 Promotes T Cell Responses through Multiple Distinct Checkpoints In Vivo, and IRF5 Immune-Mediated Disease Risk Variants Modulate These Myeloid Cell Functions.

ABSTRACT: Common IRF5 genetic risk variants associated with multiple immune-mediated diseases are a major determinant of interindividual variability in pattern-recognition receptor (PRR)-induced cytokines in myeloid cells. However, how myeloid cell-intrinsic IRF5 regulates the multiple distinct checkpoints mediating T cell outcomes in vivo and IRF5-dependent mechanisms contributing to these distinct checkpoints are not well defined. Using an in vivo Ag-specific adoptive T cell transfer approach into Irf5^-/- mice, we found that T cell-extrinsic IRF5 regulated T cell outcomes at multiple critical checkpoints, including chemokine-mediated T cell trafficking into lymph nodes and PDK1-dependent soluble Ag uptake, costimulatory molecule upregulation, and secretion of Th1 (IL-12)-

SUBMITTER: Yan J 

PROVIDER: S-EPMC7498241 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature