Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice
- Author
- Karel Van Damme (UGent) , Pieter Hertens (UGent) , Arne Martens (UGent) , Elisabeth Gilis (UGent) , Dario Priem (UGent) , Inge Bruggeman (UGent) , Amelie Fossoul (UGent) , Jozefien Declercq (UGent) , Helena Catharine Aegerter (UGent) , Andy Wullaert (UGent) , Tino Hochepied (UGent) , Esther Hoste (UGent) , Lieselotte Vande Walle (UGent) , Mohamed Lamkanfi (UGent) , Savvas Savvides (UGent) , Dirk Elewaut (UGent) , Bart Lambrecht (UGent) and Geert van Loo (UGent)
- Organization
- Project
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- Investigating itaconic acid as a critical immunometabolite in Influenza and RSV infections
- Study of the molecular pathways through which linear (de)ubiquitination governs skin inflammation and aberrant epidermal stem cell activation
- Study of microbiota-host interactions during colon cancer development using a unique microbiome dependent mouse model
- Host-microbe interaction in intestinal homeostasis: unravelling the mechanisms involved in the onset of multiple inflammation-related diseases
- Charcot Stichting - Fund 2022: Investigating itaconic acid as a critical immunometabolite in multiple sclerosis
- The impact of cell death on the cancer stem cell niche in non-melanoma skin cancer
- Novel mechanisms of inflammation and cell death regulation in autoinflammatory and infectious diseases
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Regulation of the Nlrp1a inflammasome in cutaneous and systemic autoinflammation
- Single cell analysis of inflammasome-mediated IL-1ß secretion in primary human monocytes
- The disease-modifying effect of the microbiome in a spontaneous mouse model for systemic lupus erythematosus
- Investigating the molecular mechanisms and therapeutic use of A20 and MYSM1 in inflammatory signaling and pathology
- Rational design of biologics for therapeutic development (FoldCo)
- An integrated approach to unravel eosinophil function in chronic eosinophilic disorders
- Targeting transcription factor addiction in acute leukemia (TaTFAL)
- Understanding the immunological basis of persistent airway obstruction in asthma
- Towards the structural and molecular basis of pro-inflammatory signalling assemblies mediated by IL-23 and IL-12
- Targeting NLRP3-mediated inflammation with novel chemotypes
- Unraveling the structural and functional roles of THEMIS proteins in T cell and B cell development and inflammation
- How T cell autoreactivity develops in early rheumatoid arthritis: the smoking gun hypothesis
- Abstract
- A20 serves as a critical brake on NF-kappa B-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been linked to various inflammatory disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Experimental gene knockout studies in mice have confirmed A20 as a susceptibility gene for SLE and RA. Here, we examine the significance of protein citrullination and NET formation in the autoimmune pathology of A20 mutant mice because autoimmunity directed against citrullinated antigens released by neutrophil extracellular traps (NETs) is central to the pathogenesis of RA and SLE. Furthermore, genetic variants impairing the deubiquitinase (DUB) function of A20 have been shown to contribute to autoimmune susceptibility. Our findings demonstrate that genetic disruption of A20 DUB function in A20 C103R knockin mice does not result in autoimmune pathology. Moreover, we show that PAD4 deficiency, which abolishes protein citrullination and NET formation, does not prevent the development of autoimmunity in A20 deficient mice. Collectively, these findings provide experimental confirmation that PAD4-dependent protein citrullination and NET formation do not serve as pathogenic mechanisms in the development of RA and SLE pathology in mice with A20 mutations.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HJ3YRR19Q4DBAKXCSS7S3HHQ
- MLA
- Van Damme, Karel, et al. “Protein Citrullination and NET Formation Do Not Contribute to the Pathology of A20/TNFAIP3 Mutant Mice.” SCIENTIFIC REPORTS, vol. 13, no. 1, 2023, doi:10.1038/s41598-023-45324-8.
- APA
- Van Damme, K., Hertens, P., Martens, A., Gilis, E., Priem, D., Bruggeman, I., … van Loo, G. (2023). Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice. SCIENTIFIC REPORTS, 13(1). https://doi.org/10.1038/s41598-023-45324-8
- Chicago author-date
- Van Damme, Karel, Pieter Hertens, Arne Martens, Elisabeth Gilis, Dario Priem, Inge Bruggeman, Amelie Fossoul, et al. 2023. “Protein Citrullination and NET Formation Do Not Contribute to the Pathology of A20/TNFAIP3 Mutant Mice.” SCIENTIFIC REPORTS 13 (1). https://doi.org/10.1038/s41598-023-45324-8.
- Chicago author-date (all authors)
- Van Damme, Karel, Pieter Hertens, Arne Martens, Elisabeth Gilis, Dario Priem, Inge Bruggeman, Amelie Fossoul, Jozefien Declercq, Helena Catharine Aegerter, Andy Wullaert, Tino Hochepied, Esther Hoste, Lieselotte Vande Walle, Mohamed Lamkanfi, Savvas Savvides, Dirk Elewaut, Bart Lambrecht, and Geert van Loo. 2023. “Protein Citrullination and NET Formation Do Not Contribute to the Pathology of A20/TNFAIP3 Mutant Mice.” SCIENTIFIC REPORTS 13 (1). doi:10.1038/s41598-023-45324-8.
- Vancouver
- 1.Van Damme K, Hertens P, Martens A, Gilis E, Priem D, Bruggeman I, et al. Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice. SCIENTIFIC REPORTS. 2023;13(1).
- IEEE
- [1]K. Van Damme et al., “Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice,” SCIENTIFIC REPORTS, vol. 13, no. 1, 2023.
@article{01HJ3YRR19Q4DBAKXCSS7S3HHQ,
abstract = {{A20 serves as a critical brake on NF-kappa B-dependent inflammation. In humans, polymorphisms in or near the TNFAIP3/A20 gene have been linked to various inflammatory disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Experimental gene knockout studies in mice have confirmed A20 as a susceptibility gene for SLE and RA. Here, we examine the significance of protein citrullination and NET formation in the autoimmune pathology of A20 mutant mice because autoimmunity directed against citrullinated antigens released by neutrophil extracellular traps (NETs) is central to the pathogenesis of RA and SLE. Furthermore, genetic variants impairing the deubiquitinase (DUB) function of A20 have been shown to contribute to autoimmune susceptibility. Our findings demonstrate that genetic disruption of A20 DUB function in A20 C103R knockin mice does not result in autoimmune pathology. Moreover, we show that PAD4 deficiency, which abolishes protein citrullination and NET formation, does not prevent the development of autoimmunity in A20 deficient mice. Collectively, these findings provide experimental confirmation that PAD4-dependent protein citrullination and NET formation do not serve as pathogenic mechanisms in the development of RA and SLE pathology in mice with A20 mutations.}},
articleno = {{17992}},
author = {{Van Damme, Karel and Hertens, Pieter and Martens, Arne and Gilis, Elisabeth and Priem, Dario and Bruggeman, Inge and Fossoul, Amelie and Declercq, Jozefien and Aegerter, Helena Catharine and Wullaert, Andy and Hochepied, Tino and Hoste, Esther and Vande Walle, Lieselotte and Lamkanfi, Mohamed and Savvides, Savvas and Elewaut, Dirk and Lambrecht, Bart and van Loo, Geert}},
issn = {{2045-2322}},
journal = {{SCIENTIFIC REPORTS}},
language = {{eng}},
number = {{1}},
pages = {{11}},
title = {{Protein citrullination and NET formation do not contribute to the pathology of A20/TNFAIP3 mutant mice}},
url = {{http://doi.org/10.1038/s41598-023-45324-8}},
volume = {{13}},
year = {{2023}},
}
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