Lentivirus-mediated knockdown of FcγRI (CD64) attenuated lupus nephritis via inhibition of NF-κB regulating NLRP3 inflammasome activation in MRL/lpr mice.

Lupus nephritis, one of the most serious complications of systemic lupus erythematosus (SLE), has been confirmed in a large number of clinical surveys. Current studies have suggested that inflammatory situation is generally considered to facilitate the occurrence and development of lupus nephritis. Previous research found that Fcγ receptor I (FcγRI) was compulsory for several autoimmune and inflammatory diseases, and it might be involved in the treatment of lupus nephritis. Furthermore, the possible molecular mechanism of the role of FcγRI in lupus nephritis still needs a further study. In the present study, in order to evaluate the effect of FcγRI on kidney function in lupus-prone MLR/lpr mice, FcγRI knockdown was implemented utilizing FcγRI-RNAi lentivirus. We reported that the administration of FcγRI-RNAi lentivirus (1) mainly inhibited FcγRI expression on macrophage of the kidneys, lowered the levels of urinary protein and serum anti-dsDNA antibody and prevented the impairment of renal function; (2) reduced the renal inflammatory cytokines (IL-1β and IL-18); (3) decreased NF-κB p65 nuclear migration, suppressed NOD-like receptor protein 3 (NLRP3) inflammasome activation, and finally inhibited renal inflammation. Together, these results showed the role of FcγRI on macrophages to involve in renal inflammatory response, potentially via regulating the NLRP3 inflammasome-associated signaling.