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.

Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn’s disease

“…Thus, Stutz et al and Mortimer et al reported that dephosphorylation of serine (S5 or S295) is necessary for NLRP3 activation, whereas Spalinger et al reported that dephosphorylation of a tyrosine (Y861) has this function (13,38,39). It was therefore logical to assume that CARD8 regulates NLRP3 inflammasome by affecting NLRP3 dephosphorylation.…”

A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22

“…However, the impaired expression of ATM and PFKFB3, which are also induced by anti-CD3 stimulation, in ARI PBMCs cannot be explained by stronger activation signals and suggests a novel mechanism. The phosphatase activity of PTPN22 also inhibits the signals induced by type I interferon (49), modulates macrophage polarization (50), and activates the inflammasome by dephosphorylating NLRP3 (51). A role of NLRP3 in Th cells was recently discovered (52).…”

Cellular Innate Immunity: An Old Game with New Players

“…NF-κB pathway. Signal 1-induced deubiquitination and dephosphorylation of NLRP3 by BRCC3 and PTPN22, respectively, have been proposed to be necessary for the licensing of NLRP3 [125,126] , and Ca 2+ -sensitive cAMP has been shown to act as an intracellular inhibitor of NLRP3 [127] . The second signal is less defined, but involves potassium efflux, calcium mobilization from intracellular store compartments, and the production of ROS [124] .…”