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PLC\u03b32\u2010deficient (<jats:italic>Plcg2<\/jats:italic><jats:sup>\u2013\/\u2013<\/jats:sup>) mice are also protected against experimental arthritis. This study was undertaken to test how PLC\u03b32 triggers autoantibody\u2010induced arthritis in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PLC\u03b32 was deleted from various mouse cellular lineages. Deletion efficacy and specificity were tested by immunoblotting and intracellular flow cytometry. Autoantibody\u2010induced arthritis was triggered by K\/BxN serum transfer. The role of neutrophil PLC\u03b32 was further investigated by analysis of the inflammatory exudate, competitive in vivo migration assays, and in vitro functional studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PLC\u03b32 deficiency in the entire hematopoietic compartment completely blocked autoantibody\u2010induced arthritis. Arthritis development was abrogated by deletion of PLC\u03b32 from myeloid cells or neutrophils but not from mast cells or platelets. Neutrophil infiltration was reduced in neutrophil\u2010specific PLC\u03b32\u2010deficient (<jats:italic>Plcg2<jats:sup>\u0394<\/jats:sup><\/jats:italic><jats:sup>PMN<\/jats:sup>) mice. However, this was not due to an intrinsic migration defect since <jats:italic>Plcg2<jats:sup>\u0394<\/jats:sup><\/jats:italic><jats:sup>PMN<\/jats:sup> neutrophils accumulated normally when wild\u2010type cells were also present in mixed bone marrow chimeras. Instead, the <jats:italic>Plcg2<jats:sup>\u0394<\/jats:sup><\/jats:italic><jats:sup>PMN<\/jats:sup> mutation blocked the accumulation of interleukin\u20101\u03b2, macrophage inflammatory protein 2 (MIP\u20102), and leukotriene B<jats:sub>4<\/jats:sub> (LTB<jats:sub>4<\/jats:sub>) in synovial tissues and reduced the secondary infiltration of macrophages. These findings were supported by in vitro studies showing normal chemotactic migration but defective immune complex\u2013induced respiratory burst and MIP\u20102 or LTB<jats:sub>4<\/jats:sub> release in PLC\u03b32\u2010deficient neutrophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Neutrophil PLC\u03b32 is critical for arthritis development, supposedly through the generation of the inflammatory microenvironment. PLC\u03b32\u2010expressing neutrophils exert complex indirect effects on other inflammatory cells. PLC\u03b32\u2010targeted therapies may provide particular benefit in inflammatory diseases with a major neutrophil component.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41704","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T05:55:53Z","timestamp":1614578153000},"page":"1614-1625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neutrophil Phospholipase C\u03b32 Drives Autoantibody\u2010Induced Arthritis Through the Generation of the Inflammatory Microenvironment"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1661-4635","authenticated-orcid":false,"given":"Krisztina","family":"Futosi","sequence":"first","affiliation":[{"name":"Semmelweis University School of Medicine  Budapest 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