Authors: Linda C. Burkly, Timothy S. Zheng, John Silke
Categories: Business & Economics
Type: BOOK - Published: 2016-01-21 - Publisher: Frontiers Media SA
The immune system mediates tissue responses under both physiological and pathological conditions, impacting the inflammatory, fibrogenic and regenerative components. In addition to various leukocyte subsets, it is now recognized that epithelial, endothelial and other non-hematopoietic tissue cell types actively contribute to the interplay shaping tissue responses. Further understanding the molecular pathways and mechanisms mediating these tissue responses is of great interest. In the past decade, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, FGF-inducible molecule-14 (Fn14), members of the TNF/TNFR superfamily, have emerged as a prominent molecular axis regulating tissue responses. Generally leukocyte-derived, TWEAK signals through Fn14 which is highly induced in injured and diseased tissues on the surface of parenchymal, stromal and progenitor cells, thereby orchestrating a host of tissue-shaping responses, including inflammation, angiogenesis, cell proliferation or death, and the regulation of progenitor cells. Compelling preclinical results indicate that whereas transient TWEAK/Fn14 activation promotes productive tissue responses after acute injury, excessive or persistent TWEAK/Fn14 activation drives pathological tissue responses, leading to progressive damage and degeneration in target organs of injury, autoimmune and inflammatory diseases and cancer. Given that the highly inducible pattern of Fn14 expression is well conserved between mouse and man, the role of TWEAK/Fn14 in human