Tumour Necrosis Factors

Abstract

The cytokine tumour necrosis factor (TNF) is the name‐giving member of a large ligand family mirrored by a respective family of membrane receptors. Most ligand members show a typical homotrimeric structure and exert their bioactivities as regulators of the innate and the adaptive immune system. TNF itself is a major activator of proinflammatory responses regulating natural immunity. TNF occurs both in a membrane bound form and a soluble form, both binding but differentially activating two distinct membrane receptors. TNFR1 is expressed in virtually all tissues. TNFR2 is mainly found in immune cells and also the endothelium and neuronal tissue. Both receptors activate distinct intracellular signalling pathways showing some overlap. TNFR1 initiates stimulatory and antiapoptotic signals as well as apoptotic and additional death‐inducing signals in a highly regulated manner, TNFR2 mainly activates cell proliferation and antiapoptotic signalling pathways. Key Concepts: The family of TNF ligands and receptors coordinates the complex network of immune responses. The typical TNF ligand member is a homotrimer capable to bind up to three of its respective receptors. TNF receptors possess no enzymatic activity; activation occurs via recruitment of adaptor molecules after ligand‐induced multimerisation. Most TNF receptor family members are linked to the transcription factor family of nuclear factors of kappaB (NF‐κB). Cells possess altruistic cell death programmes like apoptosis and necroptosis, which control each other. Some members of the TNF receptor superfamily carry a so‐called death domain and can induce apoptosis (and/or necroptosis). Owing to its powerful proinflammatory properties, TNF is involved in progression of many autoimmune diseases and is a major target of current clinical treatment regimens.

An algal symbiont (Breviolum psygmophilum) responds more strongly to chronic high temperatures than its facultatively symbiotic coral host (Astrangia poculata)

“…The most upregulated genes with informative annotation included a tumor necrosis factor-related protein, nitric oxide synthases, and a small heat shock protein. Tumor necrosis factor-related proteins activate proinflammatory reactions and regulate cell proliferation (Neumann et al ., 2001). Nitric oxide synthases were highly upregulated in heat-stressed aposymbiotic colonies, and were also part of the enriched KEGG relaxin signaling pathway.…”