Published February 6, 2015 | Version v1
Journal article Open

IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells

  • 1. University of California, San Diego
  • 2. Technical University Braunschweig
  • 3. University of Manchester
  • 4. University of Chicago
  • 5. University of Pennsylvania
  • 6. Jinan University

Description

IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.

Data availability

All relevant data are within the paper and its Supporting Information files except for the microarray data which is available from NCBI GEO Datasets under the accession number GSE64594.

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journal.ppat.1004635.pdf

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Additional details

Identifiers

DOI
10.1371/journal.ppat.1004635
Other
oai:uchicago.tind.io:8206

Funding

National Institutes of Health
R00-AI089935
Sidney Kimmel Foundation
Hellman Fellows
Cancer Research Institute
Irvington Postdoctoral Fellow
Deutsche Forschungsgemeinschaft
SFB 621
European Network of Excellence
MUGEN LSHG-CT-2005-005203

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics
Center(s) or Institute(s)
Institute for Genomics and Systems Biology