Oct 25, 2018

Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation

BioRxiv : the Preprint Server for Biology
Yajing GaoChandrashekhar Pasare

Abstract

Dendritic cells (DCs) are critical for priming and differentiation of pathogen-specific CD4 T cells. However, to what extent innate cues from DCs dictate transcriptional changes in T cells leading to effector heterogeneity remains elusive. Here we have used an in vitro approach to prime naive CD4 T cells by DCs stimulated with distinct pathogens. We have found that such pathogen-primed CD4 T cells express unique transcriptional profiles dictated by the nature of the priming pathogen. In contrast to cytokine-polarized Th17 cells that display signatures of terminal differentiation, pathogen-primed Th17 cells maintain a high degree of heterogeneity and plasticity. Further analysis identified caspase-1 as one of the genes upregulated only in pathogen-primed Th17 cells but not in cytokine-polarized Th17 cells. T-cell-intrinsic caspase-1, independent of its function in inflammasome, is critical for inducing optimal pathogen-driven Th17 responses. More importantly, T cells lacking caspase-1 fail to induce colitis following transfer into RAG-deficient mice, further demonstrating the importance of caspase-1 for the development of pathogenic Th17 cells in vivo . This study underlines the importance of DC-mediated priming in identifying n...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Study
In Vivo
T-Lymphocyte
Genes
CASP1 gene
Pathogenic Organism
Patient Transfer
Transcription, Genetic
Immunodeficient Mouse
Cell Differentiation Process

About this Paper

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.