PMID- 31967646
OWN - NLM
STAT- MEDLINE
DCOM- 20201106
LR  - 20201106
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 217
IP  - 4
DP  - 2020 Apr 6
TI  - Transcriptional profiling identifies caspase-1 as a T cell-intrinsic regulator of 
      Th17 differentiation.
LID - 10.1084/jem.20190476 [doi]
LID - e20190476
AB  - 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.
CI  - (c) 2020 Gao et al.
FAU - Gao, Yajing
AU  - Gao Y
AD  - Department of Immunology, University of Texas Southwestern Medical Center, 
      Dallas, TX.
AD  - Immunology Graduate Program, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Deason, Krystin
AU  - Deason K
AD  - Immunology Graduate Program, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Jain, Aakanksha
AU  - Jain A
AD  - Division of Immunobiology, Center for Inflammation and Tolerance, Cincinnati 
      Children's Hospital Medical Center, Cincinnati, OH.
AD  - Immunology Graduate Program, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Irizarry-Caro, Ricardo A
AU  - Irizarry-Caro RA
AD  - Division of Immunobiology, Center for Inflammation and Tolerance, Cincinnati 
      Children's Hospital Medical Center, Cincinnati, OH.
AD  - Immunology Graduate Program, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Dozmorov, Igor
AU  - Dozmorov I
AD  - Department of Immunology, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Coughlin, Laura A
AU  - Coughlin LA
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Rauch, Isabella
AU  - Rauch I
AD  - Department of Molecular Microbiology and Immunology, Oregon Health & Science 
      University, Portland, OR.
FAU - Evers, Bret M
AU  - Evers BM
AD  - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 
      TX.
FAU - Koh, Andrew Y
AU  - Koh AY
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, TX.
AD  - Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern 
      Medical Center, Dallas, TX.
AD  - Department of Microbiology, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Wakeland, Edward K
AU  - Wakeland EK
AD  - Department of Immunology, University of Texas Southwestern Medical Center, 
      Dallas, TX.
FAU - Pasare, Chandrashekhar
AU  - Pasare C
AD  - Division of Immunobiology, Center for Inflammation and Tolerance, Cincinnati 
      Children's Hospital Medical Center, Cincinnati, OH.
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 
      Cincinnati, OH.
LA  - eng
GR  - R01 AI113125/AI/NIAID NIH HHS/United States
GR  - R01 AI123176/AI/NIAID NIH HHS/United States
GR  - R01 GM120196/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - EC 3.4.22.36 (Casp1 protein, mouse)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1/*genetics
MH  - Cell Differentiation/*genetics
MH  - Cell Line, Tumor
MH  - Cell Polarity
MH  - Citrobacter rodentium
MH  - Colitis/genetics/metabolism
MH  - Cytokines/metabolism
MH  - Dendritic Cells/metabolism
MH  - Enterobacteriaceae Infections/metabolism/microbiology
MH  - Female
MH  - Gene Knockout Techniques
MH  - Inflammasomes/metabolism
MH  - Lymphocyte Activation/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Th17 Cells/*metabolism/*microbiology
MH  - Transcription, Genetic/*genetics
MH  - Transcriptome
PMC - PMC7144520
COIS- Disclosures: The authors declare no competing interests exist.
EDAT- 2020/01/23 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/10/06
CRDT- 2020/01/23 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/10/07 00:00 [revised]
PHST- 2019/12/09 00:00 [accepted]
PHST- 2020/01/23 06:00 [entrez]
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/10/06 00:00 [pmc-release]
AID - 133631 [pii]
AID - jem.20190476 [pii]
AID - 10.1084/jem.20190476 [doi]
PST - ppublish
SO  - J Exp Med. 2020 Apr 6;217(4):e20190476. doi: 10.1084/jem.20190476.