Regenerative capacity and the developing immune system
Regenerative capacity and the developing immune system
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DOI：
10.1007/b99966
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Neff, AW
中科院分区：
文献类型：
--
作者：
Mescher, AL;Neff, AW
脊椎动物免疫系统的许多组成部分已经进化为具有双重的相互关联的功能，既保护受损组织免受感染，又提供组织维护和损伤修复。器官再生能力在无脊椎动物和某些生殖原始的脊椎动物中很突出，但在哺乳动物中发育不良。我们已经提出，哺乳动物免疫系统的进化产生了炎症细胞相互作用的损伤部位，优化了组织防御和促进组织修复，但这些改善包括随之而来的损失的再生capability.This章简要回顾了两个再生系统的工作：无疤痕修复胎儿哺乳动物皮肤和再生的幼蛙截肢。在这两个器官中，在个体发育期间逐渐丧失了在解剖学上和功能上完整的新结构再生的潜力，并且这种丧失与在受损组织中产生炎症反应的免疫系统的发展相一致。器官再生失败长期以来一直与疤痕或纤维化有关，这种现象是损伤部位免疫细胞和成纤维细胞炎症相互作用的直接结果。综述了与修复相关的免疫的几个方面，包括抗原递呈细胞和淋巴细胞的重要性、这些细胞和其他细胞释放的相关细胞因子和生长因子、细胞外基质成分的免疫功能、和成纤维细胞的免疫功能。在各种转基因小鼠模型中的皮肤修复已经特别提供了信息。进一步研究与皮肤和两栖动物肢体再生能力丧失相关的免疫机制将有助于促进哺乳动物器官再生。
Many components of the vertebrate immune system have evolved with dual, interrelated functions of both protecting injured tissues from infection and providing for tissue maintenance and repair of injuries. The capacity for organ regeneration, prominent among invertebrates and certain phylogenically primitive vertebrates, is poorly developed in mammals. We have proposed that evolution of the mammalian immune system has produced inflammatory cellular interactions at sites of injury which have optimized tissue defense and facilitated tissue repair, but that these improvements included concomitant loss of regenerative capacity.This chapter briefly reviews work in two regenerating systems: scar-free repair of fetal mammalian skin and regeneration of amputated limbs in larval frogs. In both organs the potential to regenerate anatomically and functionally complete new structures is lost gradually during ontogeny and this loss coincides with development of an immune system producing an inflammatory response in injured tissues. Failure of organ regeneration has long been associated with scarring or fibrosis and this phenomenon is a direct result of inflammatory interactions of immune cells and fibroblasts at sites of injury.Several aspects of immunity related to repair are reviewed, including the importance of antigen-presenting cells and lymphocytes, relevant cytokines and growth factors released by these and other cells, immune functions of extracellular matrix components, and immunological functions of fibroblasts. Skin repair in various transgenic mouse models has been especially informative. Further study of immune mechanisms associated with the loss of regenerative capacity in the skin and amphibian limb will be useful for efforts to promote mammalian organ regeneration.