title: IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells.
abstract: 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.
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Hyang-Mi
authors: HM
authors: Lee
authors: Technical University Braunschweig, Braunschweig, Germany.
authors: Anne
authors: A
authors: Fleige
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Ruth
authors: R
authors: Forman
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Sunglim
authors: S
authors: Cho
authors: Department of Human Genetics, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, United States of America.
authors: Aly Azeem
authors: AA
authors: Khan
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Ling-Li
authors: LL
authors: Lin
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors: Duc T
authors: DT
authors: Nguyen
authors: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Aisling
authors: A
authors: O'Hara-Hall
authors: The First Affiliated Hospital, International Imunology Center, The Biomedical Translational Research Institute, Key Laboratory of Molecular Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong, People's Republic of China.
authors: Zhinan
authors: Z
authors: Yin
authors: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Christopher A
authors: CA
authors: Hunter
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Werner
authors: W
authors: Muller
authors: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America; Moores Cancer Center, University of California, San Diego, La Jolla, California, United States of America.
authors: Li-Fan
authors: LF
authors: Lu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma