Arthritis critically dependent on innate immune system players.
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.
Ji
Hong
H
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.
Ohmura
Koichiro
K
Mahmood
Umar
U
Lee
David M
DM
Hofhuis
Frans M A
FM
Boackle
Susan A
SA
Takahashi
Kazue
K
Holers
V Michael
VM
Walport
Mark
M
Gerard
Craig
C
Ezekowitz
Alan
A
Carroll
Michael C
MC
Brenner
Michael
M
Weissleder
Ralph
R
Verbeek
J Sjef
JS
Duchatelle
Veronique
V
Degott
Claude
C
Benoist
Christophe
C
Mathis
Diane
D
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*
D015703:Antigens, CD; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D017452:Receptors, IgG; D003165:Complement System Proteins