Skip to Main content Skip to Navigation
Journal articles

IL-26 Confers Proinflammatory Properties to Extracellular DNA

Abstract : In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors. IL-26 is a member of the IL-10 cytokine family, overexpressed in numerous chronic inflammatory diseases, in which biological activity remains unclear. We demonstrate in this study that IL-26 binds ton genomic DNA, mitochondrial DNA, and neutrophil extracellular traps, and shuttles them in the cytosol of human myeloid cells. As a consequence, IL-26 allows extracellular DNA to trigger proinflammatory cytokine secretion by monocytes, in a STING- and inflammasome-dependent manner. Supporting these biological properties, IL-10 based modeling predicts two DNA-binding domains, two amphipathic helices, and an in-plane membrane anchor in IL-26, which are structural features of cationic amphipatic cell-penetrating peptides. In line with these properties, patients with active autoantibody-associated vasculitis, a chronic relapsing autoimmune inflammatory disease associated with extensive cell death, exhibit high levels of both circulating IL-26 and IL-26-DNA complexes. Moreover, in patients with crescentic glomerulonephritis, IL-26 is expressed by renal arterial smooth muscle cells and deposits in necrotizing lesions. Accordingly, human primary smooth cells secrete IL-26 in response to proinflammatory cytokines. In conclusion Il-26 expressed in inflammatory lesions confers proinflammatory properties to DNA released by dying cells, setting up a positive amplification loop between extensive cell death and unabated inflammation.
Document type :
Journal articles
Complete list of metadatas

Cited literature [69 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01514382
Contributor : Elizabeth Bernardo <>
Submitted on : Wednesday, April 26, 2017 - 10:44:14 AM
Last modification on : Wednesday, July 8, 2020 - 3:37:22 AM

File

2017_Poli C_ J ImmunolEq7.pdf
Publication funded by an institution

Identifiers

Citation

Caroline Poli, Jean-François Augusto, Jonathan Dauvé, Clément Adam, Laurence Preisser, et al.. IL-26 Confers Proinflammatory Properties to Extracellular DNA . Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, 198 (9), pp.3650-3661. ⟨10.4049/jimmunol.1600594⟩. ⟨inserm-01514382⟩

Share

Metrics

Record views

279

Files downloads

676