The co-expression of activating and inhibitory leukocyte immunoglobulin-like receptors in rheumatoid synovium

Rheumatoid arthritis (RA) is a chronic inflammatory synovitis, with destruction of juxtaarticular cartilage and bone, likely mediated by lipid mediators, cytokines, and proteases released from inflammatory leukocytes. The mechanisms regulating leukocyte activation in rheumatoid synovium are not fully elucidated. A new family of cell surface proteins termed leukocyte immunoglobulin-like receptors (LIRs) has been shown in vitro to modulate cellular responses through immunoreceptor tyrosine-based inhibitory motifs or through association with the Fc receptor γ chain that contains immunoreceptor tyrosine-based activation motifs. We studied the expression of inhibitory and activating LIRs in the synovium of six RA patients, three osteoarthritis patients, and three controls by immunohistochemistry. The synovium from patients with early RA showed extensive expression of the inhibitory LIR-2 and the activating LIR-7 on macrophages and neutrophils. Some mast cells and endothelial cells expressed LIR-7. There was limited expression of LIRs in synovium from two patients with long-standing RA, patients with osteoarthritis, and controls. LIR-2 recognizes MHC class I molecules. We therefore suggest that LIRs may regulate the activation of infiltrating leukocytes in synovial tissue and are a potential therapeutic target.