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Because of the mutation leading to the lack of adaptor protein PSTPIP2, these animals suffer from autoinflammatory chronic multifocal osteomyelitis similar to several human syndromes. Current evidence suggests that it is driven by hyperproduction of IL-1\u03b2 by neutrophil granulocytes. In this study, we show that in addition to IL-1\u03b2, PSTPIP2 also negatively regulates pathways governing reactive oxygen species generation by neutrophil NOX2 NADPH oxidase. Pstpip2cmo neutrophils display highly elevated superoxide production in response to a range of stimuli. Inactivation of NOX2 NADPH oxidase in Pstpip2cmo mice did not affect IL-1\u03b2 levels, and the autoinflammatory process was initiated with similar kinetics. However, the bone destruction was almost completely alleviated, suggesting that dysregulated NADPH oxidase activity is a key factor promoting autoinflammatory bone damage in Pstpip2cmo mice.<\/jats:p>","DOI":"10.4049\/jimmunol.1900953","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T15:45:52Z","timestamp":1580917552000},"page":"1607-1620","source":"Crossref","is-referenced-by-count":18,"title":["Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-2666","authenticated-orcid":false,"given":"Jarmila","family":"Kralova","sequence":"first","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1066-9413","authenticated-orcid":false,"given":"Ales","family":"Drobek","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]},{"name":"Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Prochazka","sequence":"additional","affiliation":[{"name":"Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the Czech Academy of Sciences , 25242 Vestec ,","place":["Czech Republic"]},{"name":"Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences , 25242 Vestec ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7310-3487","authenticated-orcid":false,"given":"Frantisek","family":"Spoutil","sequence":"additional","affiliation":[{"name":"Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences , 25242 Vestec ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Fabisik","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]},{"name":"Faculty of Science, Charles University , 12800 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4742-3196","authenticated-orcid":false,"given":"Daniela","family":"Glatzova","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]},{"name":"Faculty of Science, Charles University , 12800 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-2634","authenticated-orcid":false,"given":"Simon","family":"Borna","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]},{"name":"Faculty of Science, Charles University , 12800 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Pokorna","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Skopcova","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Angelisova","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gregor","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biology, Institute of Molecular Genetics of the Czech Academy of Sciences , 14220 Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-0944","authenticated-orcid":false,"given":"Pavel","family":"Kovarik","sequence":"additional","affiliation":[{"name":"Max F. 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