Collaborative Research: Bioarchaeology, Osteoimmunology, and Ecoimmunology: Linking Inflammation, Life History Tradeoffs, and Biocultural Change

免疫系统和骨骼通常被视为我们生物学中独立的一部分。然而，最近的研究表明，骨骼和免疫系统之间的相互作用比以前所认为的“骨免疫”系统的一部分更多。在生命早期经历的过度炎症会导致慢性炎症，因此会影响骨骼和身体的其他部位。这个项目检查了骨骼中的免疫和炎症蛋白，它们是骨骼和免疫功能之间这种复杂关系的标志，并将它们应用于关于人类社会的生物文化过程的问题。该项目通过将骨骼病理学的传统观察与蛋白质组分析相结合来促进骨骼生物学和生物考古学方面的知识，以更好地识别可能影响过去和现在人类发病率和死亡率的炎症反应。该项目的更广泛影响包括学生培训，包括STEM中代表性不足的群体的个人；课程扩展；国际研究合作；以及与学校、社区和公众的接触。早期生命的生物应激和免疫系统的过度激活被认为产生了连锁效应，涉及表型可塑性和生活史的权衡，形成了晚年炎症和高炎症表型的偏好。该项目对骨骼炎症性疾病进行跨学科研究，将对牙周病和骨膜反应的观察与对至少四个独立的炎性蛋白生物标志物(骨钙素、巨噬细胞炎性蛋白、白细胞衍生蛋白和中性粒细胞衍生蛋白)的蛋白质组学分析结合在一起，这些个体具有推断的高炎症表型。PIs提出了关于病理过程共同发生的生物文化假说，早期生活环境在塑造免疫反应中的作用，以及社会文化动态对人类生物学的影响。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The immune system and the skeleton are often viewed as separate parts of our biology. However, recent research has revealed that the skeletal and immune systems interact more than previously appreciated as part of the “osteoimmune” system. Hyperinflammation experienced earlier in life, which can result in chronic inflammation, therefore affects the skeleton as well as other parts of the body. This project examines immune and inflammatory proteins in bone that are markers of this complex relationship between bone and immune function and applies them to questions about biocultural processes in human societies. The project advances knowledge in skeletal biology and bioarchaeology by combining traditional observations of skeletal pathology with proteomic analysis to better identify inflammatory responses that may be shaping human morbidity and mortality in the past and present. The broader impacts of the project include student training, including individuals from groups underrepresented in STEM; curriculum expansion; international research collaborations; and engagement with schools, communities, and the public. Early life biological stress and immune system over-activation are thought to produce cascading effects involving phenotypic plasticity and life history trade-offs that shape predilections for later-life inflammatory and hyperinflammatory phenotypes. This project pursues a cross-disciplinary study of skeletal inflammatory diseases, combining observations of periodontal disease and periosteal reaction with proteomic analyses of at least of four independent inflammatory protein biomarkers (osteocalcin, macrophage inflammatory proteins, leukocyte-derived proteins, and neutrophil-derived proteins) in individuals possessing an inferred hyperinflammatory phenotype. The PIs address biocultural hypotheses about the co-occurrence of pathological processes, the role of early life environments in shaping immune response, and the influence of sociocultural dynamics on human biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.