title: FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection.
abstract: The high-affinity receptor for IgG, FcgammaRI, shares its capacity to bind IgG2a immune complexes (IgG2a-IC) with the low-affinity receptor FcgammaRIII and complement factors, hampering the definition of its biological role. Moreover, in vivo, FcgammaRI is occupied by monomeric IgG2a, reducing its accessibility to newly formed IgG2a-IC. By using a variety of FcgammaR(-/-) mice, we demonstrate that in the absence of FcgammaRI, the IgG2a-IC-induced cellular processes of phagocytosis, cytokine release, cellular cytotoxicity, and antigen presentation are impaired. FcgammaRI(-/-) mice showed impaired hypersensitivity responses, strongly reduced cartilage destruction in an arthritis model, and impaired protection from a bacterial infection. We conclude that FcgammaRI contributes substantially to a variety of IgG2a-IC-dependent immune functions and immunopathological responses.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, 2333 AL Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Ioan-Facsinay
authors.forename: S J
authors.initials: SJ
authors.lastname: de Kimpe
authors.forename: S M M
authors.initials: SM
authors.lastname: Hellwig
authors.forename: P L
authors.initials: PL
authors.lastname: van Lent
authors.forename: F M A
authors.initials: FM
authors.lastname: Hofhuis
authors.forename: H H
authors.initials: HH
authors.lastname: van Ojik
authors.forename: C
authors.initials: C
authors.lastname: Sedlik
authors.forename: S A
authors.initials: SA
authors.lastname: da Silveira
authors.forename: J
authors.initials: J
authors.lastname: Gerber
authors.forename: Y F
authors.initials: YF
authors.lastname: de Jong
authors.forename: R
authors.initials: R
authors.lastname: Roozendaal
authors.forename: L A
authors.initials: LA
authors.lastname: Aarden
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: D
authors.initials: D
authors.lastname: Mosser
authors.forename: S
authors.initials: S
authors.lastname: Amigorena
authors.forename: S
authors.initials: S
authors.lastname: Izui
authors.forename: G J B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: M
authors.initials: M
authors.lastname: van Vugt
authors.forename: J G J
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: J S
authors.initials: JS
authors.lastname: Verbeek
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001886:Bordetella pertussis / Q000276:immunology*; D002356:Cartilage / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007109:Immunity / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG