Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4

Lucia Campos Carrascosa, Matthias Klein, Yohko Kitagawa, Christina Lückel, Federico Marini, Anika König, Anna Guralnik, Hartmann Raifer, Stefanie Hagner-Benes, Diana Rädler, Andreas Böck, Cholho Kang, Michael Lohoff, Holger Garn, Bianca Schaub, Friederike Berberich-Siebelt, Shimon Sakaguchi, Tobias Bopp and Magdalena Huber ()
Additional contact information
Lucia Campos Carrascosa: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Matthias Klein: Institute for Immunology, University Medical Center Mainz
Yohko Kitagawa: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University
Christina Lückel: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Federico Marini: Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz
Anika König: Institute of Pathology, University of Würzburg
Anna Guralnik: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Hartmann Raifer: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Stefanie Hagner-Benes: Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg
Diana Rädler: University Childrens’s Hospital Munich, LMU Munich
Andreas Böck: University Childrens’s Hospital Munich, LMU Munich
Cholho Kang: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Michael Lohoff: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg
Holger Garn: Institute for Laboratory Medicine and Pathobiochemistry, University of Marburg
Bianca Schaub: University Childrens’s Hospital Munich, LMU Munich
Friederike Berberich-Siebelt: Institute of Pathology, University of Würzburg
Shimon Sakaguchi: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University
Tobias Bopp: Institute for Immunology, University Medical Center Mainz
Magdalena Huber: Institute for Medical Microbiology and Hospital Hygiene, University of Marburg

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment. IRF1 occupancy correlates with decreased IRF4 abundance, suggesting an IRF1-IRF4-binding competition at the Il9 locus. Furthermore, IRF1 shapes Th9 cells with an interferon/Th1 gene signature. Consistently, IRF1 restricts the IL-9-dependent pathogenicity of Th9 cells in a mouse model of allergic asthma. Thus our study reveals that the molecular ratio between IRF4 and IRF1 balances Th9 fate, thus providing new possibilities for manipulation of Th9 differentiation.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15366 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15366

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15366

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().