Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs
Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs
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DOI：
10.1016/j.devcel.2017.11.010
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发表时间：
2017-12-18
影响因子：
11.8
通讯作者：
Kikuchi, Kazu
中科院分区：
文献类型：
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作者：
Hui, Subhra P.;Sheng, Delicia Z.;Kikuchi, Kazu
祖先促再生途径的衰减可以解释为什么人类不能有效地再生受损器官。脊椎动物谱系表现出强大的再生，包括硬骨鱼斑马鱼，提供了深入了解成年再生能力的维护。利用已建立的脊髓、心脏和视网膜再生模型，我们发现斑马鱼T-reg样（zT（reg））细胞迅速归巢到受损器官。zT（reg）细胞的条件性消融通过损害前体细胞增殖来阻断器官再生。除了调节炎症外，浸润性zT（reg）细胞通过非白细胞介素-10依赖性分泌器官特异性再生因子（Ntf 3：脊髓; Nrg 1：心脏; Igf 1：视网膜）刺激再生。重组再生因子挽救了与zT（reg）细胞耗竭相关的再生缺陷，而Foxp 3a缺陷型zTreg细胞浸润受损器官，但未能表达再生因子。我们的数据描绘了T-reg细胞在维持促再生能力方面的器官特异性作用，这些能力可能被用于各种再生疗法。
The attenuation of ancestral pro-regenerative pathways may explain why humans do not efficiently regenerate damaged organs. Vertebrate lineages that exhibit robust regeneration, including the teleost zebrafish, provide insights into the maintenance of adult regenerative capacity. Using established models of spinal cord, heart, and retina regeneration, we discovered that zebrafish T-reg-like (zT(reg)) cells rapidly homed to damaged organs. Conditional ablation of zT(reg) cells blocked organ regeneration by impairing precursor cell proliferation. In addition to modulating inflammation, infiltrating zT(reg) cells stimulated regeneration through interleukin-10-independent secretion of organ-specific regenerative factors (Ntf3: spinal cord; Nrg1: heart; Igf1: retina). Recombinant regeneration factors rescued the regeneration defects associated with zT(reg) cell depletion, whereas Foxp3a-deficient zTreg cells infiltrated damaged organs but failed to express regenerative factors. Our data delineate organ-specific roles for T-reg cells in maintaining pro-regenerative capacity that could potentially be harnessed for diverse regenerative therapies.