The intragraft microenvironment as a central determinant of chronic rejection or local immunoregulation/tolerance.
The intragraft microenvironment as a central determinant of chronic rejection or local immunoregulation/tolerance.
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DOI：
10.1097/mot.0000000000000373
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发表时间：
2017-03
影响因子：
2.2
通讯作者：
Briscoe DM
中科院分区：
文献类型：
--
作者：
Wedel J;Nakayama H;Kochupurakkal NM;Koch J;Klagsbrun M;Bielenberg DR;Briscoe DM
慢性排斥与持续的单核细胞募集、内皮激活和增殖、局部组织缺氧以及增强效应免疫反应的相关生物学有关。尽管有相似之处，但肿瘤微环境会引发抑制效应 T 细胞反应并促进局部免疫调节的信号/因子。识别同种异体移植物中缺乏的免疫调节检查点和/或分泌因子对于理解和预防慢性排斥反应非常重要。微血管内皮细胞上免疫调节分子（细胞表面和分泌的）的相对表达在排斥同种异体移植物中存在缺陷，这种缺陷在形成排斥表型方面具有重要的功能。此外，增强局部免疫调节的共抑制分子/因子的表达受到调节，细胞内调节信号或分泌因子的识别是正在进行的研究的主题。例如，信号蛋白可能与内皮细胞和调节性 T 细胞相互作用以促进局部耐受。此外，同种异体移植物微环境中的代谢物和电解质可能调节局部效应器和调节细胞反应。同种异体移植物内的多种因素塑造了局部免疫调节或促炎症的微环境。促进移植物内细胞表面或支持免疫调节的分泌分子的表达对于长期移植物存活和/或同种免疫耐受至关重要。
Chronic rejection is associated with persistent mononuclear cell recruitment, endothelial activation and proliferation, local tissue hypoxia and related biology that enhance effector immune responses. Despite similarities, the tumor microenvironment elicits signals/factors that inhibit effector T cell responses and promote local immunoregulation. The identification of immunoregulatory check points and/or secreted factors that are deficient within allografts is of great importance in the understanding and prevention of chronic rejection. The relative expression of immunomodulatory molecules (cell surface and secreted) on microvascular endothelial cells are deficient within rejecting allografts, and this deficiency is of functional importance in shaping the phenotype of rejection. Furthermore, the expression of co-inhibitory molecules/factors that enhance local immunoregulation are modulated, and the identification of intracellular regulatory signals or secreted factors are the subject of ongoing research. For example, semaphorins may interact with endothelial cells and regulatory T cells to promote local tolerance. Additionally, metabolites and electrolytes within the allograft microenvironment may regulate local effector and regulatory cell responses. Multiple factors within allografts shape the microenvironment either towards local immunoregulation or proinflammation. Promoting the expression of intragraft cell surface or secreted molecules that support immunoregulation will be critical for long-term graft survival and/or alloimmune tolerance.
淋巴细胞诱导的血管生成：移植物-VS.宿主反应的定量和敏感测定。
DOI：
10.1084/jem.141.5.1084
发表时间：
1975-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sidky YA;Auerbach R
通讯作者：
Auerbach R