Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.

Highlights d Acetylation suppresses cGAS activity d Aspirin directly acetylates cGAS d Aspirin inhibits cGAS-mediated interferon production d Aspirin alleviates DNA-induced autoimmunity in AGS mouse models and patient cells

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Ultraviolet photoelectricity based on the vicinal cut as-supplied SrTiO3 single crystals has been experimentally studied in the absence of an applied bias at room temperature. An open-circuit photovoltage of 130ps rise time and 230ps full width at half maximum was observed under the irradiation of a 355nm pulsed laser of 25ps in duration. The dependence of the photoelectric effect on the tilting angles was studied, and the optimum angle is 20.9°. Seebeck effect is proposed to elucidate the tilting angle dependence of laser-induced photovoltage. This work demonstrates the potential of SrTiO3 single crystals in ultraviolet detection.