[HTML][HTML] Arthritis critically dependent on innate immune system players

H Ji, K Ohmura, U Mahmood, DM Lee, FMA Hofhuis… - Immunity, 2002 - cell.com
H Ji, K Ohmura, U Mahmood, DM Lee, FMA Hofhuis, SA Boackle, K Takahashi, VM Holers…
Immunity, 2002cell.com
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, FcγRIII) and the complement …
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, FcγRIII) 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.
cell.com