| First Author | Spalinger MR | Year | 2016 |
| Journal | J Clin Invest | Volume | 126 |
| Issue | 5 | Pages | 1783-800 |
| PubMed ID | 27043286 | Mgi Jnum | J:234957 |
| Mgi Id | MGI:5792478 | Doi | 10.1172/JCI83669 |
| Citation | Spalinger MR, et al. (2016) NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22. J Clin Invest 126(5):1783-800 |
| abstractText | Inflammasomes form as the result of the intracellular presence of danger-associated molecular patterns and mediate the release of active IL-1beta, which influences a variety of inflammatory responses. Excessive inflammasome activation results in severe inflammatory conditions, but physiological IL-1beta 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-1beta release. In murine models, PTPN22 deficiency resulted in pronounced colitis, increased NLRP3 phosphorylation, but reduced levels of mature IL-1beta. Conversely, patients with inflammatory bowel disease (IBD) that carried an autoimmunity-associated PTPN22 variant had increased IL-1beta levels. Together, our results identify tyrosine phosphorylation as an important regulatory mechanism for NLRP3 that prevents aberrant inflammasome activation. |
