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What has the immune system got against the glomerular podocyte?

The kidney is the target of immune-mediated injury in a variety of disease situations, with the glomerulus, a specialized knot of blood vessels that acts as the basic filtering unit of the mammalian kidney, being particularly vulnerable to damage by the immune system. Inflammation of the glomerulus, glomerulonephritis (GN), can occur as an isolated phenomenon or as part of a variety of systemic inflammatory diseases. Immunosuppressive drugs that dampen the immune response non-specifically are effective in many forms of glomerular disease but the precise targets of the immune-mediated attack and the reasons for the vulnerability of the glomerulus are poorly understood. Recent advances have highlighted the importance of the podocyte, or glomerular epithelial cell, in human glomerular physiology and disease: for a comprehensive and authoritative recent review, see Pavenstadt et al. [1]. It is my purpose in this brief paper to highlight: (i) the key role of podocytes in normal glomerular physiology; (ii) the mechanisms whereby the immune system can disrupt podocytes; (iii) the potential of the podocyte to play an active role in immune responses within the kidney; and (iv) the implications for the understanding of immunologically mediated kidney disease and the design of more rational forms of therapy.