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Publication : Transcriptional profiling identifies caspase-1 as a T cell-intrinsic regulator of Th17 differentiation.

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.
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