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Mini-FH conferred enhanced protection, as compared with FH, in an ex vivo model of paroxysmal nocturnal hemoglobinuria driven by alternative pathway dysregulation. In the current study, we tested whether and how mini-FH could block another complement-mediated disease, namely periodontitis. In a mouse model of ligature-induced periodontitis (LIP), mini-FH inhibited periodontal inflammation and bone loss in wild-type mice. Although LIP-subjected C3-deficient mice are protected relative to wild-type littermates and exhibit only modest bone loss, mini-FH strikingly inhibited bone loss even in C3-deficient mice. However, mini-FH failed to inhibit ligature-induced bone loss in mice doubly deficient in C3 and CD11b. These findings indicate that mini-FH can inhibit experimental periodontitis even in a manner that is independent of its complement regulatory activity and is mediated by complement receptor 3 (CD11b\/CD18). Consistent with this notion, a complement receptor 3\u2013interacting recombinant FH segment that lacks complement regulatory activity (specifically encompassing SCRs 19 and 20; FH19\u201320) was also able to suppress bone loss in LIP-subjected C3-deficient mice. In conclusion, mini-FH appears to be a promising candidate therapeutic for periodontitis by virtue of its ability to suppress bone loss via mechanisms that both include and go beyond its complement regulatory activity.<\/jats:p>","DOI":"10.4049\/jimmunol.2300242","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T12:56:00Z","timestamp":1686574560000},"page":"453-461","source":"Crossref","is-referenced-by-count":6,"title":["The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms"],"prefix":"10.1093","volume":"211","author":[{"given":"Xiaofei","family":"Li","sequence":"first","affiliation":[{"name":"Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University , Shanghai ,","place":["China"]},{"name":"Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph Q","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , Ulm ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-5671","authenticated-orcid":false,"given":"Viviana P","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences , Toledo, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Yancopoulou","sequence":"additional","affiliation":[{"name":"Amyndas Pharmaceuticals , Glyfada, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-3271","authenticated-orcid":false,"given":"Dimitrios C","family":"Mastellos","sequence":"additional","affiliation":[{"name":"Division of Biodiagnostic Science and Technologies, Institute of Nuclear & Radiological Sciences and Technology, Energy & Safety, National Center for Scientific Research \u201cDemokritos,\u201d \u00a0 Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-5776","authenticated-orcid":false,"given":"John D","family":"Lambris","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-8852","authenticated-orcid":false,"given":"George","family":"Hajishengallis","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"2025020406034681900_r1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ni.3858","article-title":"Novel mechanisms and functions of complement","volume":"18","author":"Hajishengallis","year":"2017","journal-title":"Nat. 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