title: Decreased Th17 and antigen-specific humoral responses in CX₃ CR1-deficient mice in the collagen-induced arthritis model.
abstract: OBJECTIVE
  CX(3) CR1 is a chemokine receptor that uniquely binds to its ligand fractalkine (CX(3) CL1) and has been shown to be important in inflammatory arthritis responses, largely due to its effects on cellular migration. This study was undertaken to test the hypothesis that genetic deficiency of CX(3) CR1 is protective in the chronic inflammatory arthritis model collagen-induced arthritis (CIA). Because CX(3) CR1 is expressed on T cells and antigen-presenting cells, we also examined adaptive immune functions in this model.
  
  
  METHODS
  Autoantibody formation, clinical, histologic, T cell proliferative, and cytokine responses were evaluated in wild-type and CX(3) CR1-deficient DBA/1J mice after immunization with heterologous type II collagen (CII).
  
  
  RESULTS
  CX(3) CR1(-/-)  mice had an ∼30% reduction in arthritis severity compared to wild-type mice, as determined by 2 independent measures, paw swelling (P < 0.01) and clinical disease score (P < 0.0001). Additionally, compared to wild-type mice, CX(3) CR1(-/-)  mice had an ∼50% decrease in anti-CII autoantibody formation (P < 0.05), decreased Th17 intraarticular cytokine expression (P < 0.01 for interleukin-17 [IL-17] and P < 0.001 for IL-23), and decreased total numbers of Th17 cells in inflamed joints (P < 0.05).
  
  
  CONCLUSIONS
  Our findings indicate that CX(3) CR1 deficiency is protective in inflammatory arthritis and may have effects that extend beyond migration that involve adaptive immune responses in autoimmune disease.
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, CB 7280, 3300 Manning Drive, Chapel Hill, NC 27599, USA. tarra002@med.unc.edu
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Tarrant
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Rishi R
authors.initials: RR
authors.lastname: Rampersad
authors.forename: Denise
authors.initials: D
authors.lastname: Esserman
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Rothlein
authors.forename: Roman G
authors.initials: RG
authors.lastname: Timoshchenko
authors.forename: Marcus W
authors.initials: MW
authors.lastname: McGinnis
authors.forename: David J
authors.initials: DJ
authors.lastname: Fitzhugh
authors.forename: Dhavalkumar D
authors.initials: DD
authors.lastname: Patel
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fong
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D018450:Disease Progression; D006614:Hindlimb; D056724:Immunity, Humoral / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology*; D013264:Stifle / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine