TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26

Stephan Meller; Jeremy Di Domizio; Kui S. Voo; Heike C. Friedrich; Georgios Chamilos; Dipyaman Ganguly; Curdin Conrad; Josh Gregorio; Didier Le Roy; Thierry Roger; John E. Ladbury; Bernhard Homey; Stanley Watowich; Robert L. Modlin; Dimitrios P. Kontoyiannis; Yong Jun Liu; Stefan T. Arold; Michel Gilliet

doi:10.1038/ni.3211

T_H17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26

Stephan Meller, Jeremy Di Domizio, Kui S. Voo, Heike C. Friedrich, Georgios Chamilos, Dipyaman Ganguly, Curdin Conrad, Josh Gregorio, Didier Le Roy, Thierry Roger, John E. Ladbury, Bernhard Homey, Stanley Watowich, Robert L. Modlin, Dimitrios P. Kontoyiannis, Yong Jun Liu, Stefan T. Arold, Michel Gilliet

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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_H17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T_H17 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_H17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.

Original language	English (US)
Pages (from-to)	970-979
Number of pages	10
Journal	Nature Immunology
Volume	16
Issue number	9
DOIs	https://doi.org/10.1038/ni.3211
State	Published - Aug 19 2015

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Meller, S., Di Domizio, J., Voo, K. S., Friedrich, H. C., Chamilos, G., Ganguly, D., Conrad, C., Gregorio, J., Le Roy, D., Roger, T., Ladbury, J. E., Homey, B., Watowich, S., Modlin, R. L., Kontoyiannis, D. P., Liu, Y. J., Arold, S. T., & Gilliet, M. (2015). T_H17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nature Immunology, 16(9), 970-979. https://doi.org/10.1038/ni.3211

Meller, S, Di Domizio, J, Voo, KS, Friedrich, HC, Chamilos, G, Ganguly, D, Conrad, C, Gregorio, J, Le Roy, D, Roger, T, Ladbury, JE, Homey, B, Watowich, S, Modlin, RL, Kontoyiannis, DP, Liu, YJ, Arold, ST & Gilliet, M 2015, 'T_H17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26', Nature Immunology, vol. 16, no. 9, pp. 970-979. https://doi.org/10.1038/ni.3211

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title = "TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26",

abstract = "Interleukin 17-producing helper T cells (TH 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 TH17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 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 TH17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.",

author = "Stephan Meller and {Di Domizio}, Jeremy and Voo, {Kui S.} and Friedrich, {Heike C.} and Georgios Chamilos and Dipyaman Ganguly and Curdin Conrad and Josh Gregorio and {Le Roy}, Didier and Thierry Roger and Ladbury, {John E.} and Bernhard Homey and Stanley Watowich and Modlin, {Robert L.} and Kontoyiannis, {Dimitrios P.} and Liu, {Yong Jun} and Arold, {Stefan T.} and Michel Gilliet",

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AU - Di Domizio, Jeremy

AU - Voo, Kui S.

AU - Friedrich, Heike C.

AU - Chamilos, Georgios

AU - Ganguly, Dipyaman

AU - Conrad, Curdin

AU - Gregorio, Josh

AU - Le Roy, Didier

AU - Roger, Thierry

AU - Ladbury, John E.

AU - Homey, Bernhard

AU - Watowich, Stanley

AU - Modlin, Robert L.

AU - Kontoyiannis, Dimitrios P.

AU - Liu, Yong Jun

AU - Arold, Stefan T.

AU - Gilliet, Michel

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AB - Interleukin 17-producing helper T cells (TH 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 TH17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 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 TH17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.

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T_H17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26

Abstract

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