title: Arthritis critically dependent on innate immune system players.
abstract: K/BxN T cell receptor transgenic mice are a model of inflammatory arthritis, similar to rheumatoid arthritis. Disease in these animals is focused specifically on the joints but stems from autoreactivity to a ubiquitously expressed antigen, glucose-6-phosphate isomerase (GPI). T and B cells are both required for disease initiation, but anti-GPI immunoglobulins (Igs), alone, can induce arthritis in lymphocyte-deficient recipients. Here, we show that the arthritogenic Igs act through both Fc receptors (in particular, FcgammaRIII) and the complement network (C5a). Surprisingly, the alternative pathway of complement activation is critical, while classical pathway components are entirely dispensable. We suggest that autoimmune disease, even one that is organ specific, can occur when mobilization of an adaptive immune response results in runaway activation of the innate response.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Frans M A
authors.initials: FM
authors.lastname: Hofhuis
authors.forename: Susan A
authors.initials: SA
authors.lastname: Boackle
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: Mark
authors.initials: M
authors.lastname: Walport
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Alan
authors.initials: A
authors.lastname: Ezekowitz
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: Michael
authors.initials: M
authors.lastname: Brenner
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.forename: Veronique
authors.initials: V
authors.lastname: Duchatelle
authors.forename: Claude
authors.initials: C
authors.lastname: Degott
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007107:Immune System; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D017452:Receptors, IgG; D003165:Complement System Proteins