title: Interferon Regulatory Factor 4 controls TH1cell effector function and metabolism.
abstract: The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for TH2and TH17cell formation and controls peripheral CD8+T cell differentiation. We used Listeria monocytogenes infection to characterize the function of IRF4 in TH1responses. IRF4-/-mice generated only marginal numbers of listeria-specific TH1cells. After transfer into infected mice, IRF4-/-CD4+T cells failed to differentiate into TH1cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation. Activated IRF4-/-CD4+T cells exhibited diminished uptake of the glucose analog 2-NBDG, limited oxidative phosphorylation and strongly reduced aerobic glycolysis. Insufficient metabolic adaptation contributed to the limited proliferation and TH1differentiation of IRF4-/-CD4+T cells. Our study identifies IRF4 as central regulator of TH1responses and cellular metabolism. We propose that this function of IRF4 is fundamental for the initiation and maintenance of all THcell responses.
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Justus
authors.initials: J
authors.lastname: Mahnke
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Valéa
authors.initials: V
authors.lastname: Schumacher
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ahrens
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Käding
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
authors.forename: Lea Marie
authors.initials: LM
authors.lastname: Feldhoff
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Huber
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Raczkowski
authors.affiliation: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D000098815:T-bet Transcription Factor; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D000099218:Interferon Regulatory Factor-4; C000611649:IFNG protein, mouse