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Nat Immunol. 2015 Sep;16(9):970-9. doi: 10.1038/ni.3211. Epub 2015 Jul 13.

T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.

Author information

1
1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Dermatology, Heinrich-Heine-University Medical Faculty, Düsseldorf, Germany.
2
Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
3
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Dermatology, Heinrich-Heine-University Medical Faculty, Düsseldorf, Germany.
5
1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Department of Infectious Diseases, University Hospital CHUV, Lausanne, Switzerland.
7
School of Molecular and Cell Biology, University of Leeds, Leeds, UK.
8
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
9
Division of Dermatology, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
10
Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
11
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
12
Division of Biological and Environmental Sciences &Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
13
1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.

Abstract

Interleukin 17-producing helper T cells (T(H)17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human T(H)17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T(H)17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of T(H)17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.

Comment in

PMID:
26168081
PMCID:
PMC4776746
DOI:
10.1038/ni.3211
[Indexed for MEDLINE]
Free PMC Article

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