美国国立卫生研究院P’ng Loke和普林斯顿大学Andrea L. Graham团队合作的研究发现，遗传和环境相互作用导致野生小鼠的免疫变异。相关论文于2024年6月14日发表于国际学术期刊《自然-免疫学》杂志。

研究人员通过研究在室外圈养并感染鞭虫（寄生虫）的C57BL/6、129S1和PWK/PhJ近交系小鼠，量化了基因型和环境对免疫特征的交互影响。细胞组成是由基因型和环境之间的相互作用决定的，而细胞因子反应异质性（包括IFNγ浓度）则主要由基因型调控，并对鞭虫负担产生影响。

此外，研究还发现，其他特征，如CD44在T细胞中的表达主要由遗传调控，而在所有小鼠种系中，CD44在 B 细胞上的表达则更多地由环境影响。值得注意的是，实验室条件下的遗传差异在小鼠野化后有所减少。这些结果表明，非遗传影响因素与遗传因素相互作用造成了免疫变异和寄生虫负担。

据介绍，仍不清楚遗传和环境对个体间免疫反应变异的相对和协同作用，尽管这对进化生物学和医学都有影响。

附：英文原文

Title: Genetic and environmental interactions contribute to immune variation in rewilded mice

Author: Oyesola, Oyebola, Downie, Alexander E., Howard, Nina, Barre, Ramya S., Kiwanuka, Kasalina, Zaldana, Kimberly, Chen, Ying-Han, Menezes, Arthur, Lee, Soo Ching, Devlin, Joseph, Mondragn-Palomino, Octavio, Souza, Camila Oliveira Silva, Herrmann, Christin, Koralov, Sergei B., Cadwell, Ken, Graham, Andrea L., Loke, Png

Issue&Volume: 2024-06-14

Abstract: The relative and synergistic contributions of genetics and environment to interindividual immune response variation remain unclear, despite implications in evolutionary biology and medicine. Here we quantify interactive effects of genotype and environment on immune traits by investigating C57BL/6, 129S1 and PWK/PhJ inbred mice, rewilded in an outdoor enclosure and infected with the parasite Trichuris muris. Whereas cellular composition was shaped by interactions between genotype and environment, cytokine response heterogeneity including IFNγ concentrations was primarily driven by genotype with consequence on worm burden. In addition, we show that other traits, such as expression of CD44, were explained mostly by genetics on T cells, whereas expression of CD44 on B cells was explained more by environment across all strains. Notably, genetic differences under laboratory conditions were decreased following rewilding. These results indicate that nonheritable influences interact with genetic factors to shape immune variation and parasite burden.

DOI: 10.1038/s41590-024-01862-5

Source: https://www.nature.com/articles/s41590-024-01862-5