Search: onr:"swepub:oai:DiVA.org:uu-464303" >
NETs decorated with...
NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE
-
Georgakis, Spiros (author)
-
Gkirtzimanaki, Katerina (author)
-
Papadaki, Garyfalia (author)
-
show more...
-
Gakiopoulou, Hariklia (author)
-
Drakos, Elias (author)
-
- Eloranta, Maija-Leena (author)
- Uppsala universitet,Reumatologi
-
Makridakis, Manousos (author)
-
Kontostathi, Georgia (author)
-
Zoidakis, Jerome (author)
-
Baira, Eirini (author)
-
- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
-
Boumpas, Dimitrios T (author)
-
Sidiropoulos, Prodromos (author)
-
Verginis, Panayotis (author)
-
Bertsias, George (author)
-
show less...
-
(creator_code:org_t)
- 2021-11-08
- 2021
- English.
-
In: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:21
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
http://insight.jci.o...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Autoimmunity
- Cytokines
- Inflammation
- Lupus
- Neutrophils
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Georgakis, Spiro ...
-
Gkirtzimanaki, K ...
-
Papadaki, Garyfa ...
-
Gakiopoulou, Har ...
-
Drakos, Elias
-
Eloranta, Maija- ...
-
show more...
-
Makridakis, Mano ...
-
Kontostathi, Geo ...
-
Zoidakis, Jerome
-
Baira, Eirini
-
Rönnblom, Lars
-
Boumpas, Dimitri ...
-
Sidiropoulos, Pr ...
-
Verginis, Panayo ...
-
Bertsias, George
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Rheumatology and ...
- Articles in the publication
-
JCI Insight
- By the university
-
Uppsala University