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Dendritic cells (DCs) are professional antigen-presenting cells that play a unique role in the priming and activation of effector T cells, but under certain circumstances, they might also protect against a detrimental inflammatory response by mechanisms, which are not yet well characterized. Landmark studies by the Kurts group demonstrated that under homeostatic conditions the mouse kidney contains an extensive network of DCs that are almost exclusively localized in the tubulointerstitium, which ensures complete surveillance of the kidney, to protect it against infections ascending through the tubular system [1]. Under inflammatory conditions such as human and experimental glomerulonephritis (GN), bone marrow-derived monocytes enter the inflamed tissue and give rise to monocyte-derived DCs [2, 3] that form periglomerular rings around inflamed glomeruli [4, 5] and are capable of producing inflammatory cytokine-like tumour necrosis factor α (TNF α) [6]. Functional studies in murine models of renal diseases provide strong evidence that DCs are capable of directly instructing immune effector cells, thus orchestrating the immunological response within the kidney. Interestingly, in the early stage of nephrotoxic nephritis, a murine model of crescentic GN, DCs attenuate renal inflammation [7], whereas at later stages they mature and efficiently present antigens to CD4 T cells, thereby inducing a harmful nephritogenic Th1 immune response [8]. The potential pro-and anti-inflammatory role of DCs seems to be highly dependent on the surrounding environment and the activation status of DCs; for example, murine and human hepatic stellate cells (but not hepatocytes) prevented the activation of naive T cells by DCs in the liver [9]. However, not much is known about the influence of resident renal cells on the phenotype and functional development of renal DCs under steady-state or inflammatory conditions, in particular in humans. A better understanding could lead to new therapeutic approaches. In this issue, Kassianos et al. describe a previously underestimated cross-talk between human proximal tubular epithelial cells (PTECs) and autologous DCs. The authors isolated human PTECs from donors who underwent tumour nephrectomy, and showed that blood-derived CD14 monocytes (from autologous blood samples) cultured in vitro and matured into DCs retain an immature monocyte-like phenotype when co-cultured with human PTEC (Figure 1). Furthermore, functional characterization of these cells revealed an anti-inflammatory phenotype in terms of a decrease in inflammatory cytokine production upon TLR3 stimulation and a reduced ability to stimulate T-cell proliferation and polarization [into a potentially nephritogenic interferon (IFN)-γ producing Th1 type]. These findings and a previous study published in NDT by the same group show that PTECs are capable of directly inhibiting autologous Tand B-lymphocyte immune responses [10], indicating that PTECs interacting with infiltrating immune cells could attenuate renal inflammation. In a recent publication, Lee et al. further emphasized the potential function of tubular cells in the regulation of the inflammatory response in renal disease. The authors analysed the functional role of macrophages in the course of acute kidney injury and demonstrated that murine proinflammatory M1 macrophages can be directly modulated by murine tubular cells to express markers of the antiinflammatory M2-type macrophages, which have been shown to provide protection against an overwhelming immune response [11]. In addition, it is known that kidney tubular cells express granulocyte-macrophage colony-stimulating factor (GM-CSF), thus contributing to the maturation of resident GM-CSF receptor-expressing DCs, which are subsequently able to activate T cells and cause them to exert their pathogenic effects [12–14]. Furthermore, it has recently been shown that co-cultured, bone marrowderived DCs can acquire and process albumin that was reabsorbed by tubular cells from the ultrafiltrate. In this way, antigenic epitopes for cross-presentation to nephritogenic CD8 T cells might be generated [15]. This indicates that the interaction of tubular cells and DCs might be a two-edge sword contributing to both proand anti-inflammatory effects in kidney disease. It is therefore of central importance to better identify and

Is there a role for proximal tubular cells in regulating dendritic cell maturation and function in renal disease?