Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Footnotes
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Corrigendum Free access | 10.1172/JCI90897

NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22

Marianne R. Spalinger,1 Stephanie Kasper,1 Claudia Gottier,1 Silvia Lang,1 Kirstin Atrott,1 Stephan R. Vavricka,1,2 Sylvie Scharl,1 Tina Raselli,1 Isabelle Frey-Wagner,1 Petrus M. Gutte,3 Markus G. Grütter,3 Hans-Dietmar Beer,4 Emmanuel Contassot,4 Andrew C. Chan,5 Xuezhi Dai,6 David J. Rawlings,6 Florian Mair,7 Burkhard Becher,7 Werner Falk,8 Michael Fried,1,2 Gerhard Rogler,1,2 and Michael Scharl1,2

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Spalinger, M. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Kasper, S. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Gottier, C. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Lang, S. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Atrott, K. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Vavricka, S. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Scharl, S. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Raselli, T. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Frey-Wagner, I. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Gutte, P. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Grütter, M. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Beer, H. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Contassot, E. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Chan, A. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Dai, X. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Rawlings, D. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Mair, F. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Becher, B. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Falk, W. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Fried, M. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Rogler, G. in: PubMed | Google Scholar

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

2Zurich Center for Integrative Human Physiology and

3Institute of Biochemistry, University of Zurich, Zurich, Switzerland.

4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland.

5Department of Immunology, Genentech, San Francisco, California, USA.

6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA.

7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.

8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Find articles by Scharl, M. in: PubMed | Google Scholar

Published November 1, 2016 - More info

Published in Volume 126, Issue 11 on November 1, 2016
J Clin Invest. 2016;126(11):4388–4388. https://doi.org/10.1172/JCI90897.
Copyright © 2016, American Society for Clinical Investigation
Published November 1, 2016 - Version history
View PDF

Related article:

NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22
Marianne R. Spalinger, … , Gerhard Rogler, Michael Scharl
Marianne R. Spalinger, … , Gerhard Rogler, Michael Scharl
Research Article Gastroenterology Immunology

NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22

  • Text
  • PDF
Abstract

Inflammasomes form as the result of the intracellular presence of danger-associated molecular patterns and mediate the release of active IL-1β, which influences a variety of inflammatory responses. Excessive inflammasome activation results in severe inflammatory conditions, but physiological IL-1β secretion is necessary for intestinal homeostasis. Here, we have described a mechanism of NLRP3 inflammasome regulation by tyrosine phosphorylation of NLRP3 at Tyr861. We demonstrated that protein tyrosine phosphatase non-receptor 22 (PTPN22), variants in which are associated with chronic inflammatory disorders, dephosphorylates NLRP3 upon inflammasome induction, allowing efficient NLRP3 activation and subsequent IL-1β release. In murine models, PTPN22 deficiency resulted in pronounced colitis, increased NLRP3 phosphorylation, but reduced levels of mature IL-1β. Conversely, patients with inflammatory bowel disease (IBD) that carried an autoimmunity-associated PTPN22 variant had increased IL-1β levels. Together, our results identify tyrosine phosphorylation as an important regulatory mechanism for NLRP3 that prevents aberrant inflammasome activation.

Authors

Marianne R. Spalinger, Stephanie Kasper, Claudia Gottier, Silvia Lang, Kirstin Atrott, Stephan R. Vavricka, Sylvie Scharl, Petrus M. Gutte, Markus G. Grütter, Hans-Dietmar Beer, Emmanuel Contassot, Andrew C. Chan, Xuezhi Dai, David J. Rawlings, Florian Mair, Burkhard Becher, Werner Falk, Michael Fried, Gerhard Rogler, Michael Scharl

×

1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland. 2Zurich Center for Integrative Human Physiology and 3Institute of Biochemistry, University of Zurich, Zurich, Switzerland. 4Clinic for Dermatology, University Hospital Zurich, Zurich, Switzerland. 5Department of Immunology, Genentech, San Francisco, California, USA. 6Seattle Children’s Research Institute, Division of Immunology, Seattle, Washington, USA. 7Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. 8Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.

Original citation: J Clin Invest. 2016;126(5):1783–1800. doi:10.1172/JCI83669.

Citation for this corrigendum: J Clin Invest. 2016;126(11):4388. doi:10.1172/JCI90897.

Tina Raselli and Isabelle Frey-Wagner were inadvertently omitted from the author list. The correct author and affiliations list is above. The updated author contributions section is below.

MRS performed experiments, analyzed the data, and wrote the first draft of the manuscript. SK, CG, TR, IFW, SL, KA, and WF performed experiments and were involved in data analysis. PMG and MGG were involved in vector design and subcloning. DJR and XD generated PTPN22-619W mice. HDB and EC performed experiments in keratinocytes and were involved in data analysis and interpretation. FM and BB performed experiments. ACC corrected and approved the manuscript. SS, SRV, MF, GR, and MS were involved in acquisition of patient samples. MS and GR conceived, designed, and supervised the study. All authors wrote, corrected, and approved the manuscript.

The authors regret the errors.

Footnotes

See the related article beginning on page 1783.

Version history
  • Version 1 (November 1, 2016): Print issue publication

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Footnotes
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts