Immune Mechanisms of Alloinjury

描述（由申请人提供）：慢性肺同种异体移植排斥反应，也称为闭塞性细支气管炎综合征（BOS），是一种炎症过程，最终导致同种异体移植气道的纤维闭塞；然而，所涉及的确切机制尚不清楚。我们的初步数据表明，CCR4/配体（CCL17和CCL22）的相互作用对同种异体移植排斥的传入和传出臂都很重要。具体来说,CCR4 /配体

DESCRIPTION (provided by applicant): Chronic lung allograft rejection, also known as bronchiolitis obliterans syndrome (BOS), is an inflammatory process that ends in fibro-obliteration of the allograft airways; however the exact mechanism(s) involved are unknown. Our preliminary data demonstrates that CCR4/ligands (CCL17 and CCL22) interaction is important for both the afferent and efferent arms of allograft rejection. Specifically, CCR4/ligand biological axis in the afferent arm of alloreactivity orchestrates allosensitization by promoting: 1) the homing of naïve CD4 and CD8 T cells to secondary lymphoid tissues and 2) the intranodal interactions between CD4 helper T cell and antigen presenting cells (APC) which licenses the APC to generate allospecific CD8 T cells. The CCR4/ligand biological axis in the efferent arm of alloreactivity promotes: 1) CD4 helper T cells to maintain clonal populations of CD8 memory cells and enhances the recruitment of allospecific CD8 T cells to the allograft that eventually leads to chronic lung allograft dysfunction. Discoveries generated by this proposal will be the basis for future therapeutic trials of pharmaceutical agents that inhibit CCR4/ligands interaction with the goal of preventing/treating BOS post-lung transplantation.