斑马鱼调节性 T 细胞介导器官特异性再生程序。

Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs.

机构信息

Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.

Evolution and Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Kensington, NSW 2052, Australia; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.

出版信息

Dev Cell. 2017 Dec 18;43(6):659-672.e5. doi: 10.1016/j.devcel.2017.11.010.

DOI:10.1016/j.devcel.2017.11.010

PMID:29257949

Abstract

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-like (zT) cells rapidly homed to damaged organs. Conditional ablation of zT cells blocked organ regeneration by impairing precursor cell proliferation. In addition to modulating inflammation, infiltrating zT 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 cell depletion, whereas Foxp3a-deficient zT cells infiltrated damaged organs but failed to express regenerative factors. Our data delineate organ-specific roles for T cells in maintaining pro-regenerative capacity that could potentially be harnessed for diverse regenerative therapies.

摘要

祖先进化的促再生途径的衰减可能解释了为什么人类不能有效地再生受损器官。包括硬骨鱼斑马鱼在内的具有强大再生能力的脊椎动物谱系，为维持成年再生能力提供了线索。我们利用已建立的脊髓、心脏和视网膜再生模型，发现斑马鱼 T 样（zT）细胞迅速归巢到受损器官。条件性消融 zT 细胞通过损害前体细胞增殖来阻止器官再生。除了调节炎症外，浸润的 zT 细胞还通过白细胞介素 10 非依赖性分泌器官特异性再生因子（Ntf3：脊髓；Nrg1：心脏；Igf1：视网膜）来刺激再生。重组再生因子挽救了与 zT 细胞耗竭相关的再生缺陷，而 Foxp3a 缺陷型 zT 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 细胞在维持促再生能力方面的器官特异性作用，这可能为各种再生治疗方法提供了潜在的应用。