Chasing the recipe for a pro-regenerative immune system.
Chasing the recipe for a pro-regenerative immune system.
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DOI：
10.1016/j.semcdb.2016.08.008
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发表时间：
2017-01
影响因子：
7.3
通讯作者：
Rosenthal NA
中科院分区：
文献类型：
--
作者：
Godwin JW;Pinto AR;Rosenthal NA
迄今为止，人类实现完美组织再生所需的关键成分和基本过程的鉴定仍然难以捉摸。脊椎动物的损伤诱导了强制性的伤口反应，这种反应将先于或重叠任何再生特定程序或疤痕结果。这个过程塑造了组织的细胞和分子景观，影响了内源性修复途径的成功或潜在的临床干预。免疫细胞的参与也需要发展的各个方面延伸到最初的炎症阶段的伤害。现在，从两栖动物、鱼类和哺乳动物的组织损伤模型中可以清楚地看出，免疫反应的类型和参与损伤部位的免疫细胞的特征可以作为决定伤口修复质量的看门人。先天免疫细胞群和适应性免疫细胞群之间的异质性，以及这些细胞的发育起源，构成了影响下游修复和纤维化抑制潜力的关键因素。免疫细胞（如巨噬细胞和T细胞）与干细胞和间充质细胞之间的细胞间相互作用对于形成这一过程至关重要，而这些交换反过来又受到损伤类型、组织位置和生物体发育阶段的影响。在发育方面，小鼠心脏再生仅限于出生后生命的早期阶段，此时先天免疫细胞与适应性免疫细胞之间的平衡可能趋于再生。在损伤的成年小鼠肝脏中，特异性巨噬细胞亚群可促进修复，而其他骨髓来源的细胞可加重损伤。其他使用基因多样化小鼠的研究表明，某些菌株的再生能力增强，但仅限于特定组织。这种增强的修复与胰岛素样生长因子-1 （IGF-1）和激活素（Act 1）等基因的表达有关，这两种基因在塑造免疫系统中都起着重要作用。免疫细胞现在被认为对再生成功所需的关键细胞类型有强大的影响。组织再生的制胜配方很可能最终通过识别限制或允许内在潜能的遗传因素和特定细胞群而找到。这对于开发人类组织再生的治疗策略至关重要。
Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding. It has now become clear from amphibian, fish and mammalian models of tissue injury that the type of immune response and the profile of immune cells attending the site of injury can act as the gatekeepers that determine wound repair quality. The heterogeneity among innate and adaptive immune cell populations, along with the developmental origin of these cells, form key ingredients affecting the potential for downstream repair and the suppression of fibrosis. Cell-to-cell interactions between immune cells, such as macrophages and T cells, with stem cells and mesenchymal cells are critically important for shaping this process and these exchanges, are in turn influenced by the type of injury, tissue location and developmental stage of the organism. Developmentally, mouse cardiac regeneration is restricted to early stages of postnatal life where the balance of innate to adaptive immune cells may be poised towards regeneration. In the injured adult mouse liver, specific macrophage subsets improve repair while other bone marrow derived cells can exacerbate injury. Other studies using genetically diverse mice have shown enhanced regeneration in certain strains, restricted to specific tissues. This enhanced repair is linked with expression of genes such as Insulin-like Growth Factor- 1 (IGF-1) and activin (Act 1), that both play important roles in shaping the immune system. Immune cells are now appreciated to have powerful influences on critical cell types required for regeneration success. The winning recipe for tissue regeneration is likely to be found ultimately by identifying the genetic elements and specific cell populations that limit or allow intrinsic potential. This will be essential for developing therapeutic strategies for tissue regeneration in humans.