Human LTBR ELISA Matched Antibody Pair

The cytokines lymphotoxin (LT) alpha, beta and their receptor (LT beta R) belong to the tumor necrosis factor (TNF) superfamily, whose founder-TNF alpha-was initially discovered due to its tumor necrotizing activity. LT beta R signaling serves pleiotropic functions including the control of lymphoid organ development, support of efficient immune responses against pathogens due to maintenance of intact lymphoid structures, induction of tertiary lymphoid organs, liver regeneration or control of lipid homeostasis. Signaling through LTbR comprises the noncanonical/canonical nuclear factor-kappa B (NF-kappa B) pathways thus inducing chemokine, cytokine or adhesion molecule expression, cell proliferation and cell survival. Blocking LT beta R signaling or Fc gamma-receptor mediated immunoablation of LT-expressing cells was demonstrated to be beneficial in various infectious or noninfectious inflammatory or autoimmune disorders. Only recently, LT beta R signaling was shown to initiate inflammation-induced carcinogenesis, to influence primary tumorigenesis and to control reemergence of carcinoma in various cancer models through distinct mechanisms. Indeed, LT beta R signaling inhibition has already been used as efficient anti-inflammatory, anti-cancer therapy in some experimental models. Here, we review the pleiotropic functions attributed to LT, the effects of its deregulation and extensively discuss the recent literature on LT's link to carcinogenesis. Oncogene (2010) 29, 5006-5018; doi:10.1038/onc.2010.260; published online 5 July 2010

The mouse lymph node (LN) can provide a niche to grow metanephric kidney to maturity. Here, we show that signaling through the lymphotoxin-beta receptor (LT beta R) is critical for kidney organogenesis both in the LN and the omentum. By transplanting kidney rudiments either in the LNs of mice undergoing LT beta R antagonist treatment or in the omenta of Ltbr knockout (Ltbr(-/-)) mice, the host LT beta R signals were found to be crucial for obtaining a well-vascularized kidney graft. Indeed, defective LT beta R signaling correlated with decreased expression of endothelial and angiogenic markers in kidney grafts as well as structural alterations. Because the number of glomerular endothelial cells expressing the LT beta R target nuclear factor kappa B-inducing kinase (NIK) decreased in the absence of a functional LT beta R, it was speculated that an LT beta R/NIK axis mediated the angiogenetic signals required for successful ectopic kidney organogenesis, given the established role of NIK in neovascularization. However, the transplantation of kidney rudiments in omenta of Nik(-/)(-) mice revealed that NIK is dispensable for ectopic kidney vascular integration and maturation. Finally, defective LT beta R signaling impaired compensatory glomerular adaptation to renal mass reduction, indicating that kidney regeneration approaches, besides whole kidney reconstruction, might benefit from the presence of LT beta R signals.