Collaborative Research: Immune tradeoffs during tissue regeneration in mammals

为什么蝾螈可以重新长出被截肢的肢体，而人类却不能？了解有利于组织再生而不是组织修复的机制仍然是生物学中悬而未决的重大问题之一。一个特别有趣的假设是，高等脊椎动物再生能力的丧失与强适应性免疫反应的存在是一致的，尽管研究很少。现在，最近在野生非洲棘鼠（Acomys）中发现了完全的组织再生，而在一种同时发生的啮齿动物（Myomyscus）中却未能再生，这使得对野生、病原体暴露和完全免疫的成年哺乳动物的免疫和再生之间的联系进行了全面的检查。具体来说，本研究验证了这样一个假设，即在(1)先天与适应性和(2)亲抗炎轴上的免疫权衡是这些野生物种之间再生能力和速度变化的基础。在细胞和分子水平上对损伤反应的免疫和炎症变化进行量化，有望揭示再生细胞中对先天免疫和抗炎分子的偏好，以及非再生细胞中对适应性免疫和促炎反应的转变。项目结果将为限制哺乳动物再生能力的机制提供基本的见解。因为再生生物学是一个迷人的话题，有很大的潜力激发学生对科学的兴趣，研究人员将吸引所有年龄段的美国和国际学生参与这个项目。来自美国的研究生和本科生将前往开展动物工作的肯尼亚，积极参与这项研究，并与肯尼亚学生和科学家合作。该项目团队还将对肯尼亚当地的一所女子中学和一所小学进行一系列访问，以展示利用非洲多刺小鼠作为工具的再生生物学的基本概念。这项研究的国际部分是由美国国家科学基金会国际和综合活动办公室共同支持的。

Why can salamanders re-grow amputated limbs but humans cannot? Understanding the mechanisms that favor tissue regeneration in lieu of tissue repair remains one of the great unanswered questions in biology. A particularly intriguing hypothesis, though poorly investigated, is that the loss of regenerative capacity in higher vertebrates coincides with the presence of a strong adaptive immune response. Now, the recent discovery of complete tissue regeneration in wild African spiny mice (Acomys) compared to the failure to regenerate in a co-occurring rodent (Myomyscus), allows a comprehensive examination of the links between immunity and regeneration in wild, pathogen-exposed, and fully immunocompetent adult mammals. Specifically, this study tests the hypothesis that tradeoffs in immunity along (1) innate vs. adaptive and (2) pro vs. anti-inflammatory axes underlie variation in the ability and rate of regeneration between these wild species. Quantifying immune and inflammatory changes at the cellular and molecular level in response to injury is expected to reveal a bias towards innate immunity and anti-inflammatory molecules in regenerators, and a shift towards adaptive immunity and pro-inflammatory responses in non-regenerators. Project results will provide fundamental insight into the mechanisms that constrain regenerative ability in mammals. Because regeneration biology is a fascinating topic with great potential to excite students about science, the investigators will engage U.S. and international students of all ages in the project. Graduate and undergraduate students from the U.S. will travel to Kenya, where animal work will take place, to actively participate in the study and collaborate with Kenyan students and scientists. The project team will also make a series of visits to a local Kenyan girls' secondary school and a primary school to showcase basic concepts in regeneration biology using African spiny mice as a tool. The international component of this study is co-supported by NSF's Office of International and Integrative Activities.