TNF Receptor-1
TNF signals through two receptors with distinct functions, TNFR1 and TNFR2. The approved anti-TNF biologics inhibit activation of both the pro-inflammatory and cytotoxic TNF receptor 1 (TNFR1) and the largely anti-inflammatory and tissue-protective TNF receptor 2 (TNFR2).
Pioneering work of two Greek scientists, Kassiotis and Kollias, published in 2001 in JEM (193:427) and JCI (107:1507), shed light for the first time on the importance of uncoupling the TNFR1- and TNFR2-TNF signaling pathways, proposing that specific blockade of TNFR1 signaling could offer advantageous novel therapeutic approaches as they would suppress the TNF pro-inflammatory activity, leaving unaffected its TNFR2-dependent immunosuppressive activity. In the following years, indeed TNFR1 emerged as an attractive target towards ameliorating the detrimental effects of the TNF signalling pathway and various TNFR1 inhibitors are currently under development or in clinical trials.
