title: Exacerbation of type II collagen-induced arthritis in apolipoprotein E-deficient mice in association with the expansion of Th1 and Th17 cells.
abstract: OBJECTIVE
  To explore the bidirectional relationship between the development of rheumatoid arthritis (RA) and atherosclerosis using bovine type II collagen (CII)-immunized B10.RIII apoE(-/-) mice, a murine model of spontaneous atherosclerosis and collagen-induced arthritis (CIA).
  
  
  METHODS
  Male B10.RIII apoE(-/-) mice and wild-type controls were immunized with 150 μg of CII emulsified in Freund's complete adjuvant (CFA). The clinical, radiologic, and histopathologic severity of CIA, the levels of circulating IgG1 and IgG2a anti-CII antibodies, the expression of proinflammatory and antiinflammatory cytokines in the joints, and the percentages of Th1, Th17, and Treg lymphocytes in the draining lymph nodes were evaluated during CIA induction. In addition, the size of atherosclerotic lesions was assessed in these mice 8 weeks after CIA induction.
  
  
  RESULTS
  B10.RIII apoE(-/-) mice that were immunized with CII and CFA developed an exacerbated CIA that was accompanied by increased joint expression of multiple proinflammatory cytokines and by the expansion in the draining lymph nodes of Th1 and Th17 cells. In contrast, the size of vascular lesions in B10.RIII apoE(-/-) mice was not affected by the development of CIA.
  
  
  CONCLUSIONS
  Our findings indicate that a deficiency in apolipoprotein E and/or its consequences in cholesterol metabolism act as accelerating factors in autoimmunity by promoting Th1 and Th17 inflammatory responses.
authors.affiliation: Universidad de Cantabria-IFIMAV, Santander, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Postigo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Genre
authors.forename: Marcos
authors.initials: M
authors.lastname: Iglesias
authors.forename: Maigualida
authors.initials: M
authors.lastname: Fernández-Rey
authors.forename: Luis
authors.initials: L
authors.lastname: Buelta
authors.forename: José
authors.initials: J
authors.lastname: Carlos Rodríguez-Rey
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism; D003094:Collagen / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology*; D058504:Th17 Cells / Q000473:pathology*
chemical_list: D000906:Antibodies; D001057:Apolipoproteins E; D016207:Cytokines; D003094:Collagen; D002784:Cholesterol