Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, Pisa, Italy.
Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Front Immunol. 2020 Jul 14;11:1485. doi: 10.3389/fimmu.2020.01485. eCollection 2020.
Novel methods in immunological research and microbiome evaluation have dramatically changed several paradigms associated with the pathogenesis of allergic asthma (AAS). Ovalbumin and house dust mite-induced AAS in germ-free or specific pathogen-free mice are the two leading experimental platforms that significantly contribute to elucidate the relationship between AAS and gut microbiota. Beyond the exacerbation of T helper (Th) 2 responses, a complex network of immunological interaction driven by gut microbiota could modulate the final effector phase. Regulatory T cells are abundant in gastrointestinal mucosa and have been shown to be pivotal in AAS. The gut microbiota could also influence the activity of other T cell subsets such as Th9, Th17, and populations of effector/memory T lymphocytes. Furthermore, gut microbiota metabolites drive the hematopoietic pattern of dendritic cells and ameliorate lung Th2 immunity in AAS models. The administration of probiotics has shown conflicting results in AAS, and limited evidence is available on the immunological pathways beyond their activity. Moreover, the impact of early-life gut dysbiosis on AAS is well-known both experimentally and clinically, but discrepancies are observed between preclinical and clinical settings. Herein, our aim is to elucidate the most relevant preclinical and clinical scenarios to enlighten the potential role of the gut microbiota in modulating T lymphocytes activity in AAS.
新型免疫研究方法和微生物组评估方法极大地改变了与过敏性哮喘(AAS)发病机制相关的几个范式。无特定病原体(GF)或特定病原体(SPF)小鼠卵白蛋白和屋尘螨诱导的 AAS 是两个主要的实验平台,为阐明 AAS 与肠道微生物组之间的关系做出了重要贡献。除了加剧辅助性 T 细胞(Th2)反应之外,肠道微生物组驱动的复杂免疫相互作用网络还可以调节最终效应阶段。调节性 T 细胞在胃肠道黏膜中丰富,并已被证明在 AAS 中具有关键作用。肠道微生物组还可以影响其他 T 细胞亚群的活性,如 Th9、Th17 和效应/记忆 T 淋巴细胞群体。此外,肠道微生物组代谢物驱动树突状细胞的造血模式,并改善 AAS 模型中的肺 Th2 免疫。益生菌的给药在 AAS 中显示出相互矛盾的结果,并且关于其活性之外的免疫途径的证据有限。此外,早期肠道失调对 AAS 的影响在实验和临床中都得到了很好的证明,但在临床前和临床环境中观察到差异。在此,我们的目的是阐明最相关的临床前和临床情况,以阐明肠道微生物组在调节 AAS 中 T 淋巴细胞活性方面的潜在作用。