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The inhibitory receptor FcγRII reduces joint inflammation in immune complex arthritis not only by inhibition of activatory FcγR but also by efficient clearance of immune complexes
Arthritis Res Ther volume 5, Article number: 112 (2003)
In earlier studies, we found that using FcγRII-/- mice, the inhibiting FcγRII is an important regulator of joint inflammation and cartilage destruction during immune-complex arthritis (ICA) and that this receptor probably acts by down-regulating activatory FcγR functions.
In the present study, we investigated the in vivo role of FcγRII during ICA in the absence of activatory FcγR, using FcγRI/III-/- and FcγRI/II/III-/- mice.
At day 3 after ICA induction, a strongly elevated inflammation (exudate and infiltrate respectively 2200% and 270%) was found in knee joints of FcγRI/II/III-/- as determined by histology whereas inflammation was almost absent in knee joints of FcγRI/III-/-. Eight hours after injection of heat-aggregated IgG, significantly more IgG was detected in knee joints of FcγRI/II/III-/- in comparison with wild-type controls which was mainly associated with the lining layer. Although inflammation was much higher in knee joints of FcγRI/II/III-/- and the inflammatory cells still expressed an inflammatory phenotype, severe cartilage destruction (matrix-metalloproteinase-mediated neoepitopes in the matrix and chondrocyte death) was completely prevented, in contrast to the marked destruction observed in the wild type.
Our study indicates that FcγRII reduces joint inflammation in the absence of activating FcγR by promoting clearance of immune complexes from the joint. Infiltrating cells that fail to express FcγR, although they still become activated, are no longer able to induce cartilage destruction.
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van Lent, P., Nabbe, K., Blom, A. et al. The inhibitory receptor FcγRII reduces joint inflammation in immune complex arthritis not only by inhibition of activatory FcγR but also by efficient clearance of immune complexes. Arthritis Res Ther 5, 112 (2003) doi:10.1186/ar742
- Knee Joint
- Immune Complex
- Inhibitory Receptor
- Joint Inflammation
- Cartilage Destruction