First Author | Gao Y | Year | 2020 |
Journal | J Exp Med | Volume | 217 |
Issue | 4 | PubMed ID | 31967646 |
Mgi Jnum | J:289537 | Mgi Id | MGI:6432704 |
Doi | 10.1084/jem.20190476 | Citation | Gao Y, et al. (2020) Transcriptional profiling identifies caspase-1 as a T cell-intrinsic regulator of Th17 differentiation. J Exp Med 217(4) |
abstractText | Dendritic cells (DCs) are critical for the differentiation of pathogen-specific CD4 T cells. However, to what extent innate cues from DCs dictate transcriptional changes in T cells remains elusive. Here, we used DCs stimulated with specific pathogens to prime CD4 T cells in vitro and found that these T cells express unique transcriptional profiles dictated by the nature of the priming pathogen. More specifically, the transcriptome of in vitro C. rodentium-primed Th17 cells resembled that of Th17 cells primed following infection in vivo but was remarkably distinct from cytokine-polarized Th17 cells. We identified caspase-1 as a unique gene up-regulated only in pathogen-primed Th17 cells and discovered a critical role for T cell-intrinsic caspase-1, independent of inflammasome, in optimal priming of Th17 responses. T cells lacking caspase-1 failed to induce colitis or confer protection against C. rodentium infection due to suboptimal Th17 cell differentiation in vivo. This study underlines the importance of DC-mediated priming in identifying novel regulators of T cell differentiation. |