Development of proteoglycan-induced arthritis is critically dependent on Fcγ receptor type III expression




To study the necessity for activating Fcγ receptor types I and III (FcγRI and FcγRIII) in proteoglycan-induced arthritis (PGIA), a murine model of rheumatoid arthritis, and to determine whether usage of FcγRI or FcγRIII correlates with the Th1 phenotype or the autoantibody isotype in PGIA.


PGIA was induced by immunizing FcγRI−/−, FcγRIII−/−, and wild-type (WT) littermate mice with human PG. The development and severity of arthritis were monitored over time. PG-specific T cell interleukin-2 (IL-2) production and B cell antibody responses were assessed. FcγRIII blocking antibodies were used to inhibit arthritis in an adoptive transfer system. Inflammation in the hind paws was evaluated by assessing cytokine and chemokine messenger RNA (mRNA) transcripts by real-time polymerase chain reaction.


FcγRI−/− mice developed arthritis with similar kinetics and severity as WT littermate controls, whereas FcγRIII−/− mice failed to develop the disease. Both FcγRI−/− and FcγRIII−/− mice produced similar amounts of PG-specific antibody and IL-2 as littermate controls. Transfer of arthritis was successfully blocked in mice treated with a blocking antibody against FcγRIII. FcγRIII−/− mice displayed a significant decrease in cytokine and chemokine mRNA transcripts obtained from the hind paws of immunized mice, whereas FcγRI−/− mice demonstrated a similar increase in cytokine and chemokine transcripts as controls.


These results demonstrate that FcγRIII expression is critical to the development of PGIA, and usage of FcγRIII correlates with the IgG1 isotype of the PG-specific antibody response. FcγRIII expression appears to be important in the effector phase of arthritis, possibly by activating cytokine- and chemokine-secreting cells in the joint.