Laboratory mice housed in the natural environment identifies genetic and environmental contributions to immune variation

The relative contribution of genetic and environmental factors to variation in immune response is still poorly understood. Here, we performed a deep phenotypic analysis of immunological parameters and molecular profiles of laboratory mice released into an outdoor enclosure, carrying genetic susceptibility genes (Nod2 and Atg16l1) implicated in the development of inflammatory bowel diseases. Differences in lymphocyte populations were largely driven by the lab and wild environment. However, cytokine production after stimulation with microbial antigens showed a stronger genetic component in the lab, which was reduced after exposure to the wild environment. Multi-omic models identified key transcriptional factors associated with lymphocyte changes predictive of the environment, as well as sub-networks associated with cytokine responses against Candida albicans and Bacteroides vulgatus. Hence, exposing laboratory mice of different genetic backgrounds to the outdoor environment may identify important contributors to immune variation. Bulk transcriptome of mesenteric lymph nodes from laboratory and rewilded mice

遗传与环境因素对免疫应答变异的相对贡献，目前仍未得到充分阐明。本研究针对携带与炎症性肠病发生发展相关的遗传易感基因（Nod2及Atg16l1）、被释放至室外围栏的实验小鼠，开展了免疫学参数与分子谱的深度表型分析。淋巴细胞群的差异主要由实验室环境与野生环境主导。然而，经微生物抗原刺激后的细胞因子产生量在实验室环境中表现出更强的遗传相关性，该相关性在小鼠暴露于野生环境后有所减弱。多组学模型鉴定出了与可预测环境的淋巴细胞变化相关的关键转录因子，以及与针对白色念珠菌（Candida albicans）和普通拟杆菌（Bacteroides vulgatus）的细胞因子应答相关的基因子网络。因此，将不同遗传背景的实验小鼠暴露于室外环境，或可阐明免疫变异的关键影响因素。实验小鼠与回归野生环境小鼠的肠系膜淋巴结批量转录组（bulk transcriptome）