{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:27:24Z","timestamp":1790018844029,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The role of complement in the etiology of Sjo\u0308gren\u2019s syndrome (SjS), a human autoimmune disease manifested primarily by salivary and lacrimal gland dysfunction resulting in dry mouth\/dry eye syndrome, remains ill-defined. In the present study, we examined the role of complement component-3 (C3) using a newly constructed C3-gene knockout mouse, C57BL\/6.NOD-Aec1Aec2.C3\u2212\/\u2212. Inactivation of C3 in the parental C57BL\/6.NOD-Aec1Aec2 strain, a model of primary SjS, resulted in a diminished or total absence of both preclinical and clinical manifestations during development and onset of disease, including reduced acinar cell apoptosis, reduced levels of caspase-3, lack of leukocyte infiltration of submandibular glands, reduced synthesis of disease-associated autoantibodies, maintenance of normal glandular architecture, and retention of normal saliva secretion. In addition, C57BL\/6-NOD.Aec1Aec2.C3\u2212\/\u2212 mice did not exhibit increased numbers of marginal zone B cells, a feature of SjS-prone C57BL\/6-NOD.Aec1Aec2 mice. Interestingly, C57BL\/6-NOD.Aec1Aec2.C3\u2212\/\u2212 mice retained some early pathological manifestations, including activation of serine kinases with proteolytic activity for parotid secretory protein. This improvement in the clinical manifestations of SjS-like disease in C57BL\/6.NOD-Aec1Aec2.C3\u2212\/\u2212 mice, apparently a direct consequence of C3 deficiency, supports a much more important role for complement in the adaptive autoimmune response than previously recognized, possibly implicating an essential role for innate immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.179.4.2318","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T18:56:09Z","timestamp":1397847369000},"page":"2318-2329","source":"Crossref","is-referenced-by-count":46,"title":["Development of Sjo\u0308gren\u2019s Syndrome in Nonobese Diabetic-Derived Autoimmune-Prone C57BL\/6.NOD-\n                    <i>Aec1Aec2<\/i>\n                    Mice Is Dependent on Complement Component-3"],"prefix":"10.1093","volume":"179","author":[{"given":"Cuong Q","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuna","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet G","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammon B","family":"Peck","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida , Gainesville, FL 32610"},{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL 32610"},{"name":"Center for Orphan Autoimmune Diseases, College of Dentistry, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,8,15]]},"reference":[{"key":"2026012809193964600_R1","first-page":"517","volume-title":"Rheum. 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