This conclusion is also supported by our human data showing CASP1 mRNA induction only in the tubulointerstitium, where most of the NLRP3 inflammasome-related genes are found to be induced in human nephropathies and where renal dendritic cells reside . It is intriguing to speculate that the lack of IL-1b secretion by glomerular cells protects the glomerulus from inappropriate inflammation potentially induced by immune complexes, hyperglycemia, oxidative stress, or immunostimulatory crystals. The rationale for testing the role of NLRP3-ASC-and caspase-1 was based on the phenotype of Il-1r- and Il-18-deficient mice upon antiserum injection. However, lack of the IL-1R only partially reduced glomerular damage. The IL-1R ligates IL-1a in additionompartment of patients with systemic lupus erythematosus , IGAN, and anti-neutrophil cytoplasmatic antibody -positive, rapidly progressive glomerulonephritis a significant up regulation compared to controls could be observed, while in glomeruli no significant change was seen. Together, genes that are related to the NLRP3- ASC-caspase-1 axis are induced during progressive glomerulonephritis but only in the tubulointerstitium and not in the glomerular compartment of the kidney . to IL-1b, which may involve an NLRP3- or caspase-1-independent IL-1R agonist that contributes to glomerular pathology and it plays a major role in cell death-induced inflammation . In fact, IL-1a was shown to contribute to the humoral pathways of immune complex glomerulonephritis . IL-18-deficiency had no significant effect on glomerular pathology and only partially reduced tubular atrophy which may relate to a proinflammatory role of IL-18 in this compartment. Our data are in contrast to the documented role of IL-18 BEZ235 signaling in spontaneous lupus-like immune complex glomerulonephritis of MRLlpr mice . Still, glomerular inflammation in heterologous anti-GBM disease involves innate rather than adaptive immunity given that the model was MyD88- but not Rag2-dependent. Since injury in this model was previously shown to involve TLR2 and TLR4 we assume that the TLR2/MyD88 and the TLR4/MyD88 pathways predominate for the induction of innate immunity in this model of acute glomerulonephritis. In summary, heterologous anti-GBM nephritis develops independently of the NLRP3-ASC-caspase-1 axis likely due to an inability for glomerular cells to induce and to secrete IL-1b. Renal dendritic cells secrete IL-1b upon NLRP3 activation mainly in the tubulointerstitial compartment. We therefore conclude that the capacity for triggering innate immunity inside the kidney is Nutlin-3 manufacturer compartment-specific. The lack of IL-1b and IL-18 secretion by glomerular cells is another mechanism that prevents inappropriate glomerular inflammation and damage.