Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs.
Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs.
复制标题
血红素加氧酶-1 对于移植器官至关重要并促进对移植器官的耐受性。
DOI：
10.1096/fj.05-4791fje
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Bach,FritzH
中科院分区：
文献类型：
--
作者：
Yamashita,Kenichiro;Ollinger,Robert;McDaid,James;Sakahama,Hideyasu;Wang,Hongjun;Tyagi,Shivraj;Csizmadia,Eva;Smith,NealR;Soares,MiguelP;Bach,FritzH
This investigation focused on obtaining a further understanding of the role of heme oxygenase‐1 (HO‐1) in tolerance induction. Hearts from C57BL/6 (H‐2b) mice survived long‐term when transplanted into BALB/c (H‐2d) recipients treated with the tolerance‐inducing regimen of anti‐CD40L antibody (MR‐1) plus donor‐specific transfusion (DST). Grafts did not, however, survive long‐term in (HO‐1−/−) recipients given the same treatment. Similarly, long‐term survival induced by DST was ablated when HO‐1 activity was blocked by zinc protoporphyrin IX (ZnPPIX). We further asked whether modulation of HO‐1 expression/activity could be used to promote the induction of graft tolerance. DST alone (day 0) failed to promote any prolongation of survival of DBA/2 (H‐2d) hearts transplanted into B6AF1 (H‐2b,k/d) recipients. However, long‐term survival and (dominant peripheral) tolerance were readily induced when DST was combined with induction of HO‐1 expression by cobalt protoporphyrin IX (CoPPIX). HO‐1 induction plus DST led to a significant up‐regulation ofFoxp3, TGF‐β, IL‐10, and CTLA4, which suggests a prominent role for CD4+CD25+regulatory T cells (Tregs). In fact, the tolerogenic effect of HO‐1 plus DST was dependent on CD4+CD25+Tregs as suggested by adoptively transferring these cells into irradiated recipients under various regimens. Taken together, these findings show that expression of HO‐1 in a graft recipient can be essential for long‐term graft survival and for induction of tolerance and that modulation of HO‐1 expression/activity can be used therapeutically to synergize in the generation of graft tolerance.
