Targeting iNKT cells for the treatment of sickle cell disease. Clin Immunol 2011 Aug;140(2):177-83
Date
03/25/2011Pubmed ID
21429807Pubmed Central ID
PMC3328191DOI
10.1016/j.clim.2011.03.002Scopus ID
2-s2.0-79960442267 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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.
Author List
Field JJ, Nathan DG, Linden JAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine A2 Receptor AntagonistsAnemia, Sickle Cell
Animals
Clinical Trials as Topic
Humans
Lymphocyte Activation
Mice
Natural Killer T-Cells
Purines
Pyrazoles
