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美國國立衛生研究院P’ng Loke和普林斯頓大學Andrea L. Graham團隊合作的研究發現，遺傳和環境相互作用導致野生小鼠的免疫變異。相關論文于2024年6月14日發表于國際學術期刊《自然-免疫學》雜志。

研究人員通過研究在室外圈養并感染鞭蟲（寄生蟲）的C57BL/6、129S1和PWK/PhJ近交系小鼠，量化了基因型和環境對免疫特征的交互影響。細胞組成是由基因型和環境之間的相互作用決定的，而細胞因子反應異質性（包括IFNγ濃度）則主要由基因型調控，并對鞭蟲負擔產生影響。

此外，研究還發現，其他特征，如CD44在T細胞中的表達主要由遺傳調控，而在所有小鼠種系中，CD44在 B 細胞上的表達則更多地由環境影響。值得注意的是，實驗室條件下的遺傳差異在小鼠野化后有所減少。這些結果表明，非遺傳影響因素與遺傳因素相互作用造成了免疫變異和寄生蟲負擔。

據介紹，仍不清楚遺傳和環境對個體間免疫反應變異的相對和協同作用，盡管這對進化生物學和醫學都有影響。

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

期刊信息

Nature Immunology：《自然—免疫學》，創刊于2000年。隸屬于施普林格·自然出版集團，最新IF：31.25

官方網址：https://www.nature.com/ni

投稿鏈接：https://mts-ni.nature.com/cgi-bin/main.plex