The Friend leukaemia virus integration 1 ( F li‐1) transcription factor affects lupus nephritis development by regulating inflammatory cell infiltration into the kidney

Summary The transcription factor Friend leukaemia virus integration 1 ( F li‐1) is implicated in the pathogenesis of systemic lupus erythematosus in both human patients and murine models of lupus. M urphy R oths large ( MRL )/ lpr mice and N ew Z ealand mixed ( NZM )2410 mice, murine models of lupus, with decreased expression of F li‐1 had significantly prolonged survival and reduced nephritis. Lupus nephritis is a major cause of mortality and morbidity in patients, and inflammatory cell infiltration plays a key role in the development of the disease. To study how the expression of F li‐1 affects the infiltration of inflammatory cells into the kidneys, we generated congenic enhanced green fluorescent protein ( GFP ) transgenic MRL / lpr mice. A significantly increased number of GFP ‐expressing inflammatory cells infiltrated the kidneys of wild‐type MRL / lpr mice compared to F li‐1 heterozygous ( F li‐1 +/− ) MRL / lpr mice after injection of GFP + cells. Expression of inflammatory chemokine mRNA, including chemokine ( C ‐ C motif) ligand ( CCL )2, CCL 3, CCL 4 and CCL 5, was significantly lower in the kidneys from F li‐1 +/− MRL / lpr mice compared to wild‐type littermates. Numbers of infiltrated cells into the kidneys correlate with expression levels of CCL 2, CCL 4 and CCL 5, but not the titres of anti‐ds DNA autoantibodies in these mice. Significantly increased inflammatory cells from wild‐type MRL / lpr mice infiltrated into kidneys compared to the cells from F li‐1 +/− MRL / lpr mice. The chemotaxis of inflammatory cells from F li‐1 +/− MRL / lpr mice towards each chemokine was decreased significantly compared to inflammatory cells from wild‐type MRL / lpr mice in the transwell migration assay in vitro . Our results indicate that F li‐1 affects lupus nephritis development by regulating the expression of chemokines in the kidney and the migration of inflammatory cells.