Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin ? receptor (LT?R) signaling is crucial for the formation of lymphoid tissue, and inhibition of LT?R signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LT?R signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LT? and LT? ligands, as well as LT?R. The LT?R protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LT? was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LT? and LT? mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LT?R signaling. Importantly, in a murine lupus model, LT?R blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LT?R signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.     «

Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin ? receptor (LT?R) signaling is crucial for the formation of lymphoid tissue, and inhibition of LT?R signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LT?R signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LT? and LT? ligands, as well...     »