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NETs decorated with...
NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE
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Georgakis, Spiros (författare)
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Gkirtzimanaki, Katerina (författare)
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Papadaki, Garyfalia (författare)
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Gakiopoulou, Hariklia (författare)
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Drakos, Elias (författare)
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- Eloranta, Maija-Leena (författare)
- Uppsala universitet,Reumatologi
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Makridakis, Manousos (författare)
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Kontostathi, Georgia (författare)
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Zoidakis, Jerome (författare)
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Baira, Eirini (författare)
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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Boumpas, Dimitrios T (författare)
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Sidiropoulos, Prodromos (författare)
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Verginis, Panayotis (författare)
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Bertsias, George (författare)
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(creator_code:org_t)
- 2021-11-08
- 2021
- Engelska.
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Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:21
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://insight.jci.o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33-decorated NETs that stimulate robust IFN-α synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. IL33-silenced neutrophil-like cells cultured under lupus-inducing conditions generated NETs with diminished interferogenic effect. Importantly, NETs derived from patients with SLE are enriched in mature bioactive isoforms of IL-33 processed by the neutrophil proteases elastase and cathepsin G. Pharmacological inhibition of these proteases neutralized IL-33-dependent IFN-α production elicited by NETs. We believe these data demonstrate a novel role for cleaved IL-33 alarmin decorating NETs in human SLE, linking neutrophil activation, type I IFN production, and end-organ inflammation, with skin pathology mirroring that observed in the kidneys.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- Autoimmunity
- Cytokines
- Inflammation
- Lupus
- Neutrophils
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Georgakis, Spiro ...
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Gkirtzimanaki, K ...
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Papadaki, Garyfa ...
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Gakiopoulou, Har ...
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Drakos, Elias
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Eloranta, Maija- ...
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visa fler...
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Makridakis, Mano ...
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Kontostathi, Geo ...
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Zoidakis, Jerome
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Baira, Eirini
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Rönnblom, Lars
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Boumpas, Dimitri ...
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Sidiropoulos, Pr ...
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Verginis, Panayo ...
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Bertsias, George
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Reumatologi och ...
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JCI Insight
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Uppsala universitet