R&D Systems Recombinant Mouse Lymphotoxin beta R/TNFRSF3 Fc Chimera, CF (50 UG) Item ID: RDS1008LR050

Lymphotoxin  beta R (LT beta R), previously called TNF RIII or TNF R‑related protein (TNF Rrp), is a type I transmembrane glycoprotein within the TNF receptor superfamily, designated TNFRSF3 (1, 2). Mouse LT beta R cDNA encodes 415 amino acids (aa) including a 30 aa signal peptide, a 193 aa extracellular domain (ECD), a 21 aa transmembrane domain, and a 171 aa cytoplasmic domain. The ECD contains four cysteine‑rich motifs characteristic of the TNF receptor superfamily (1). Within the ECD, mouse LT beta R shares aa sequence identity of 91% aa with rat, and 65-71% with human, canine, porcine, equine and bovine LT beta R. Soluble LT beta R can be formed by proteolytic cleavage of the ECD, and is an inhibitor of transmembrane LT beta R, as is recombinant LT beta R, which inhibits autoimmunity (2-5). A potential mouse isoform that ends at aa 218, just prior to the transmembrane domain, could also be secreted and inhibitory (6). LT beta R is expressed by visceral, lymphoid, and other stroma, epithelia and myeloid cells, but not lymphocytes (1, 3). LT beta R ligands include homotrimers of LIGHT (TNFSF14; also a ligand for HVEM) and the heterotrimeric lymphotoxin LT alpha 1/ beta 2 (2, 3, 5). Depending on the cell type and expression of TRAF3, activation of LT beta R has been shown to induce canonical (IKK/RelA; pro‑inflammatory) or alternative (NIK/RelB; lymphoid organogenic) NF kappa B activation (5, 7). LT beta R is expressed on mesenchymal stromal organizing cells that give rise to stroma of primary (thymus), secondary (tonsils, lymph nodes and Peyers patches) and tertiary (ectopic inflammatory) lymphoid structures (2-4, 8-10). Secondary immune tissues are absent in LT beta R‑deficient mice (2-4). LT beta R engagement induces production of IL‑7, RANK, TRANCE/RANK L, VEGF‑C, adhesion molecules such as VCAM‑1, ICAM‑1 and MAdCAM, and chemokines such as CXCL13, CCL19 and CCL21 (2, 8-10). LT beta R is expressed by hepatocytes, is up-regulated in regeneration, hepatitis and hepatocellular carcinoma, and influences lipid metabolism and atherosclerosis (3, 5, 11). It regulates cell growth and can initiate inflammation‑related carcinogenesis (5, 11).