Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Tyck till om SwePub Sök här!

Search: WFRF:(Syvänen Ann Christine 1950 ) > Tandre Karolina > Mattsson Johan > Genetic variations ...

1 of 1
Previous record
Next record
To hitlist

Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus

Odqvist, Lina (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Jevnikar, Zala (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Riise, Rebecca (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Öberg, Lisa (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Rhedin, Magdalena (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Leonard, Dag, 1975- (author): Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Yrlid, Linda (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Jackson, Sonya (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Mattsson, Johan (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Nanda, Sambit (author): University of Dundee,Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland

Cohen, Philip (author): University of Dundee,Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland

Knebel, Axel (author): University of Dundee,Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland

Arthur, Simon (author): University of Dundee,Univ Dundee, Sch Life Sci, Div Immunol & Cell Signaling, Dundee, Scotland

Thörn, Kristofer (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Svenungsson, Elisabet (author): Karolinska Institutet,Karolinska Institute,Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

Jönsen, Andreas (author): Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden

Gunnarsson, Iva (author): Karolinska Institutet,Karolinska Institute,Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

Tandre, Karolina (author): Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Alexsson, Andrei (author): Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Kastbom, Alf (author): Linköpings universitet,Linköping University,Linkoping Univ, Dept Rheumatol, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland

Rantapää-Dahlqvist, Solbritt (author): Umeå universitet,Umeå University,Reumatologi,Umea Univ, Med Fak, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden

Eloranta, Maija-Leena (author): Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Syvänen, Ann-Christine, 1950- (author): Uppsala universitet,Uppsala University,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Bengtsson, Anders (author): Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden

Johansson, Patrik (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Discovery Sci, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Sandling, Johanna K. (author): Uppsala universitet,Uppsala University,Science for Life Laboratory, SciLifeLab,Reumatologi,Uppsala Univ, Sweden

Sjöwall, Christopher (author): Linköpings universitet,Linköping University,Linkoping Univ, Dept Rheumatol, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland

Rönnblom, Lars (author): Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden

Collins, Barry (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden,AstraZeneca RandD Gothenburg, Sweden

Vaarala, Outi (author): AstraZeneca R&D Gothenburg, BioPharmaceut R&D, Res & Early Dev, Resp Inflammat & Autoimmune, Molndal, Sweden;MedImmune LLC, Resp Inflammat & Autoimmun Dept, Gaithersburg, MD 20878 USA,AstraZeneca RandD Gothenburg, Sweden; MedImmune LLC, MD 20878 USA

show less...

(creator_code:org_t)

2019-07-12
2019
English.
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:10, s. 1363-1370

Related links:: http://dx.doi.org/10... (free); show more...; https://ard.bmj.com/...; https://doi.org/10.1...; https://umu.diva-por... (primary) (Raw object); https://uu.diva-port... (primary) (Raw object); https://liu.diva-por... (primary) (Raw object); https://lup.lub.lu.s...; https://doi.org/10.1...; https://urn.kb.se/re...; https://urn.kb.se/re...; http://kipublication...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objectives: Genetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis. Methods: CRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A KI cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926. Results: Genetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes. Conclusions: We propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.

Subject headings

NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

NET
PAD4
PADI4
peptidyl arginine deiminase
rs2230926

Publication and Content Type

art (subject category)
ref (subject category)

Find in a library

Annals of the Rheumatic Diseases (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

Articles in the publication: Annals of the Rh ...

By the university: Lund University; Umeå University; Uppsala University; Karolinska Institutet; Linköping University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se