NLRP3 tyrosine phosphorylation is controlled by protein tyrosine phosphatase PTPN22

Abstract

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.

An update on cell intrinsic negative regulators of the NLRP3 inflammasome

“…Indeed, phosphorylated NLRP3 was shown to be sequestered in the autophagosomes in LPS + MSU‐treated BMDC, and that the phosphorylated NLRP3 recovered from autophagsome enriched fractions were significantly increased in Ptpn22 ‐deficient BMDC . PTPN22 interacted with NLRP3 upon MDP, MSU, and ATP‐induced NLRP3 inflammasome activation in LPS‐primed THP1, MM6, BMDC and PBMC, and dephosphorylated Tyrosine‐861 on NLRP3 . Although these studies did not elucidate the kinases that phosphorylate Tyrosine‐861, it is clear that the kinase has to be a tyrosine kinase .…”

“…Several studies have reported phosphorylation of NLRP3 as a potential mechanism that negatively regulates inflammasome activation. NLRP3 dephosphorylation by protein tyrosine phosphatase, non‐receptor Type 22 (PTPN22) was reported to be critical for activation of the NLRP3 inflammasomes and induction of DSS‐induced colitis in mice, suggesting phosphorylation as the limiting step for NLRP3 inhibition . Indeed, phosphorylated NLRP3 was shown to be sequestered in the autophagosomes in LPS + MSU‐treated BMDC, and that the phosphorylated NLRP3 recovered from autophagsome enriched fractions were significantly increased in Ptpn22 ‐deficient BMDC .…”

Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders

“…Phosphorylation of NLRP3 can occur at its residues of PYD, LRR domain, and the linker PYD and NACHT, which either inhibits or activates its expression. Phosphorylation of different amino acid residues of NLRP3 inhibited NLRP3 inflammasome activation, such as serine 3 (S3) and tyrosine 861 (Y861) . Py et al.…”

Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling

“…A recent study revealed a critical function of PTPN22 in the robust activation of NLRP3 inflammasome and IL‐1β secretion. PTPN22 interactions directly with NLRP3 and dephosphorylates NLRP3 at Tyr861 leading to NLRP3 inflammasome activation 59 . It was noted that patients with inflammatory bowel disease who carried the gain‐of‐function variants of PTPN22 showed increased IL‐1β levels in intestinal biopsy and serum samples.…”

“…It was noted that patients with inflammatory bowel disease who carried the gain‐of‐function variants of PTPN22 showed increased IL‐1β levels in intestinal biopsy and serum samples. Thus, tyrosine phosphorylation at NLRP3 (by an undetermined kinase) is an important regulatory mechanism for inhibiting aberrant NLRP3 inflammasome assembly 59 . Syk and Jnk are additional important kinases that contribute to the activation of caspase‐1 related to the NLRP3 and AIM2 inflammasomes 60 .…”