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Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno\u2010inflammatory consequences. In the present study, we found that circulating NET\u2010related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180\u2010NC16A immune complexes\u2010induced NETosis in neutrophils from BP patients, which was abrogated by Fc\u03b3 receptor and\/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B\u2010cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.<\/jats:p>","DOI":"10.1096\/fj.202100145r","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T03:52:16Z","timestamp":1624247536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Neutrophil extracellular traps contribute to immune dysregulation in bullous pemphigoid via inducing B\u2010cell differentiation and antibody production"],"prefix":"10.1096","volume":"35","author":[{"given":"Hui","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Dermatology Xijing Hospital Fourth Military Medical University Xi'an 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