title: Reverse signaling through the co-stimulatory ligand, CD137L, as a critical mediator of sterile inflammation.
abstract: CD137 (also called 4-1BB and TNFRSF9) has recently received attention as a therapeutic target for cancer and a variety of autoimmune and inflammatory diseases. Stimulating CD137 in vivo enhances CD8(+) T cell-activity and results in strong immunosuppression in some contexts. This paradoxical phenomenon may be partially explained by the ability of CD137-stimulating reagents (usually agonistic monoclonal antibodies against CD137) to overactivate T cells and other CD137-expressing cells. This over-activity is associated with deleting pathogenic T cells and B cells or generating a tolerogenic microenvironment. Recent studies, however, suggest that the biology of CD137 and its ligand (CD137L) are more complex, mainly due to bidirectional signaling between CD137 and CD137L. For example, signaling through CD137L in non-hematopoietic cells such as epithelial cells and endothelial cells has been shown to play an essential role in sterile inflammation by regulating immune cell recruitment. One outstanding, and clinically important, issue is understanding how bidirectional signaling through CD137 and CD137L controls the vicious cycle of sterile inflammation (e.g., ischemia-reperfusion tissue injury and meta-inflammatory diseases).
authors.affiliation: Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan 682-714, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Hong Rae
authors.initials: HR
authors.lastname: Cho
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism / Q000502:physiology*; D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D053330:4-1BB Ligand; D018836:Inflammation Mediators; C505974:TNFSF9 protein, human; D051193:Toll-Like Receptors