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Individuals carrying the NLRC4-H443P mutation show exacerbated inflammation upon exposure to a cold environment due to caspase-1 hyperactivation. The mechanism of cold-induced hyperactivation of caspase-1 by none of the FCAS-causing mutants is known. We identified heat shock cognate protein 70 (HSC70) as an interacting partner of NLRC4-H443P that negatively regulates caspase-1 activation. Exposure to subnormal temperature reduces interaction of H443P with HSC70, causing caspase-1 hyperactivation. We provide a molecular mechanism for exacerbation of inflammation induced by cold temperature in individuals carrying the NLRC4-H443P mutation, which might have broader implications for temperature regulation of FCAS-causing mutations of other receptors.<\/jats:p>","DOI":"10.1073\/pnas.1905261116","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T20:06:12Z","timestamp":1570651572000},"page":"21694-21703","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4"],"prefix":"10.1073","volume":"116","author":[{"given":"Akhouri Kishore","family":"Raghawan","sequence":"first","affiliation":[{"name":"CSIR-Centre for Cellular and Molecular Biology, Hyderabad-500007, 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