ATP and T-cell-mediated rejection

被引:18
|
作者
Castillo-Leon, Eduardo [1 ]
Dellepiane, Sergio [1 ]
Fiorina, Paolo [1 ,2 ,3 ]
机构
[1] Harvard Med Sch, Boston Childrens Hosp, Nephrol Div, 300 Longwood Ave,Enders Bldg,5th Floor En511, Boston, MA 02115 USA
[2] Univ Milan, Fdn Romeo & Enrica Invernizzi, Pediat Clin Res Ctr, Dept Biomed & Clin Sci L Sacco,Int Ctr T1D, Milan, Italy
[3] ASST Fatebenefratelli Sacco, Div Endocrinol, Milan, Italy
关键词
alloimmune T cells; ATP; purinergic system; rejection; transplantation; ISCHEMIA-REPERFUSION INJURY; ADENOSINE A(2A) RECEPTOR; VERSUS-HOST-DISEASE; BRILLIANT BLUE FCF; VIVO LUNG PERFUSION; VEIN GRAFT MARKING; P2X7; RECEPTOR; PURINERGIC RECEPTORS; EXTRACELLULAR ATP; LONG-TERM;
D O I
10.1097/MOT.0000000000000484
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review Purine nucleosides and nucleotides are released in the extracellular space following cell injury and act as paracrine mediators through a number of dedicated membrane receptors. In particular, extracellular ATP (eATP) significantly influences T-lymphocyte activation and phenotype. The purpose of this review is to discuss the role of ATP signaling in the T-cell-mediated alloimmune response. Recent findings In various animal models of solid transplantation, the purinergic axis has been targeted to prevent acute rejection and to promote long-term graft tolerance. The inhibition of ATP-gated P2X receptors has been shown to halt lymphocyte activation, to downregulate both Th1 and Th17 responses and to promote T-regulatory (Treg) cell differentiation. Similarly, the inhibition of ATP signaling attenuated graft-versus-host disease in mice undergoing hematopoietic cell transplantation. Significantly, different drugs targeting the purinergic system have been recently approved for human use and may be a viable therapeutic option for transplant patients. Summary The inhibition of eATP signaling downregulates the alloimmune response, expands Treg cells and promotes graft survival. This robust preclinical evidence and the recent advances in pharmacological research may lead to intriguing clinical applications.
引用
收藏
页码:34 / 43
页数:10
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