title: Targeting iNKT cells for the treatment of sickle cell disease.
abstract: Sickle cell disease (SCD) causes widely disseminated vaso-occlusive episodes. Building on evidence implicating invariant NKT (iNKT) cells in the pathogenesis of ischemia/reperfusion injury, recent studies demonstrate that blockade of iNKT cell activation in mice with SCD reduces pulmonary inflammation and injury. In patients with SCD, iNKT cells in blood are increased in absolute number and activated in comparison to healthy controls. iNKT cell activation is reduced by agonists of adenosine 2A receptors (A(2A)Rs) such as the clinically approved coronary vasodilator, regadenoson. An ongoing multi-center, dose-finding and safety trial of infused regadenoson, has been initiated and is providing preliminary data about its safety and efficacy to treat SCD. Very high accumulation of adenosine may have deleterious effects in SCD through activation of adenosine 2B receptors that are insensitive to regadenoson. Future possible therapeutic approaches for treating SCD include selective A(2B)R antagonists and antibodies that deplete iNKT cells.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Field
authors.forename: David G
authors.initials: DG
authors.lastname: Nathan
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D011687:Purines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D011687:Purines; D011720:Pyrazoles; C430916:regadenoson