title: Janus kinase-3 (JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation.
abstract: Current immunosuppressive therapy in clinical organ transplantation is based on drugs that suppress various functions of immunocompetent cells but still affect cells and organ compartments other than the immune system. Hence, these drugs have considerable side effects which lead to increased morbidity and reduced life-quality of transplant recipients. A major step forward in the rationale design of clinical immunosuppression resides in the elucidation of molecular targets that play a critical role specifically within the immune system. Recently, Janus kinase 3 (JAK3) has been identified as such a molecule. Genetic absence or ablation of this tyrosine kinase is associated with defective T-cell immunity that results in severe combined immunodeficiency (SCID) without apparent changes in other organ systems. Furthermore, pharmacological inhibition has significantly prolonged allograft survival in several experimental models of organ transplantation. The present review provides an overview of the emerging role of JAK3 in the immune system and the development of JAK3-inhibiting drugs. The potential clinical application of JAK3 inhibitors in organ transplantations is discussed in the light of a recent series of successful kidney transplantations in non-human primates immunosuppressed solely with a novel JAK3 inhibitor.
authors.affiliation: Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria. marcus.saemann@meduniwien.ac.at
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053616:Janus Kinase 3; D016377:Organ Transplantation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014184:Transplantation, Homologous
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3