RT Journal Article
SR Electronic
T1 Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 452763
DO 10.1101/452763
A1 Yajing Gao
A1 Krystin Deason
A1 Aakanksha Jain
A1 Ricardo A Irizarry-Caro
A1 Igor Dozmorov
A1 Isabella Rauch
A1 Edward K Wakeland
A1 Chandrashekhar Pasare
YR 2018
UL http://biorxiv.org/content/early/2018/10/25/452763.abstract
AB Our study revealed that DCs shape distinct pathogen-specific CD4 T cell transcriptome and from which, we discovered an unexpected role for T-cell-intrinsic caspase-1 in promoting Th17 differentiation.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 naïve 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 novel regulators of T cell differentiation.