Rapid Evolution of Primate Type 2 Immune Response Factors Linked to Asthma Susceptibility
Rapid Evolution of Primate Type 2 Immune Response Factors Linked to Asthma Susceptibility
复制标题
DOI：
10.1093/gbe/evx120
复制
发表时间：
2017-06-01
影响因子：
3.3
通讯作者：
Elde, Nels C.
中科院分区：
文献类型：
--
作者：
Barber, Matthew F.;Lee, Elliott M.;Elde, Nels C.
宿主免疫途径在病原体的拮抗作用下进化迅速。微生物感染还会引发过度炎症，导致各种自身免疫性疾病，包括哮喘、狼疮、糖尿病和关节炎。免疫系统进化和人类自身免疫性疾病之间的确切联系尚不清楚。在这里，我们提供的证据表明，在灵长类血统中，2型免疫反应途径的几个组成部分受到了反复的正向选择。值得注意的是，中枢免疫调节因子IL13的替换对应于与人类哮喘易感性有关的多态。我们还发现了嗜酸性粒细胞颗粒蛋白之间氨基酸替代加速以及基因获得和丢失事件的证据，嗜酸性粒细胞颗粒蛋白作为有毒的抗菌效应器，通过破坏呼吸道组织促进哮喘病理。这些结果支持这样一种假设，即与病原体的进化冲突促进了在动物进化过程中对日益强大的免疫反应的权衡。我们的发现也与自然选择导致自身免疫性疾病等位基因在人类中传播的观点一致。
Host immunity pathways evolve rapidly in response to antagonism by pathogens. Microbial infections can also trigger excessive inflammation that contributes to diverse autoimmune disorders including asthma, lupus, diabetes, and arthritis. Definitive links between immune system evolution and human autoimmune disease remain unclear. Here we provide evidence that several components of the type 2 immune response pathway have been subject to recurrent positive selection in the primate lineage. Notably, substitutions in the central immune regulator IL13 correspond to a polymorphism linked to asthma susceptibility in humans. Wealso find evidence of accelerated amino acid substitutions as well as gene gain and loss events among eosinophil granule proteins, which act as toxic antimicrobial effectors that promote asthma pathology by damaging airway tissues. These results support the hypothesis that evolutionary conflicts with pathogens promote tradeoffs for increasingly robust immune responses during animal evolution. Our findings are also consistent with the view that natural selection has contributed to the spread of autoimmune disease alleles in humans.