Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome.

Podocyte foot processes (FP) and the interposed slit diaphragms (SD) form the final barrier to protein loss, explaining why podocyte injury is typically associated with marked proteinuria (1). The highly dynamic FP actin cytoskeleton is linked to the SD and proteins that regulate podocyte actin dynamics therefore are of critical importance for structural maintenance and sustained function of the glomerular filter. We recently made the novel finding that under pathologic conditions, with FP effacement and proteinuria, podocytes upregulate B7-1 (2). B7-1 (also termed CD80) is a transmembrane protein expressed on the surface of B cells and other antigen-presenting cells (APC). On B cells and other APC, B7-1 provides a co-stimulatory signal for T cells through binding to its receptors CD28 and CTLA-4 (3–5). The immune function of B7-1 has been well described (3–5). To explore the function of B7-1 in podocytes, we developed a novel, unique murine model of LPS-induced, B7-1–dependent transient nephrotic syndrome that shares several key features of human minimal-change disease (MCD) (2). On the basis of our observations, we propose that LPS induces transient B7-1–dependent nephrotic syndrome through the reorganization of the podocyte FP actin cytoskeleton and disruption of the SD (2). Our findings suggest a novel function for B7-1 in danger signaling by podocytes (2).