Our previous study had demonstrated that oral administration of Houttuynia cordata polysaccharides (HCP) without in vitro antiviral activity ameliorated gut and lung injuries induced by influenza A virus (IAV) in mice. However, as macromolecules, HCP was hard to be absorbed in gastrointestinal tract and had no effect on lung injury when administrated intravenously. The action mechanism of HCP was thus proposed as regulating the gut mucosal-associated lymphoid tissue (GALT). Actually, HCP treatment restored the balance of Th17/Treg cells firstly in GALT and finally in the lung. HCP reduced the expression of chemokine CCL20 in the lung and regulated the balance of Th17/Treg carrying CCR6+ (the CCL20 receptor), which was associated with specific migration of Th17/Treg cells from GALT to lung. In vitro, HCP inhibited Th17 cell differentiation through the downregulation of phospho-STAT3, whereas it promoted Treg cell differentiation by upregulating phospho-STAT5. Furthermore, its therapeutic effect was abolished in RORγt-/- or Foxp3-/- mice. These findings indicated that oral administration of macromolecular polysaccharides like HCP might ameliorate lung injury in IAV infected mice via directly regulating the balance of Th17/Treg cells in gut-lung axis. Our results provided a potential mechanism underlying the therapeutic effect of polysaccharides on pulmonary infection.

中文翻译：

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调节肠肺轴中Th17 / Treg细胞的平衡有助于鱼腥草多糖对H1N1引起的急性肺损伤的治疗作用。

我们以前的研究表明，口服鱼腥草多糖（HCP）而没有体外抗病毒活性可减轻小鼠的由甲型流感病毒（IAV）引起的肠道和肺部损伤。然而，作为大分子，HCP难以在胃肠道中吸收，静脉内给药对肺损伤没有影响。因此，提出了HCP的作用机制是调节肠黏膜相关淋巴样组织（GALT）。实际上，HCP治疗首先在GALT中，最后在肺中恢复了Th17 / Treg细胞的平衡。HCP降低了肺中趋化因子CCL20的表达并调节了带有CCR6 +的Th17 / Treg的平衡（CCL20受体），这与Th17 / Treg细胞从GALT到肺的特异性迁移有关。体外，HCP通过下调磷酸STAT3抑制Th17细胞分化，而通过上调磷酸STAT5促进Treg细胞分化。此外，在RORγt-/-或Foxp3-/-小鼠中其治疗作用被取消。这些发现表明口服大分子多糖如HCP可能通过直接调节肠肺轴Th17 / Treg细胞的平衡来减轻IAV感染小鼠的肺损伤。我们的结果提供了潜在的机制，多糖对肺部感染的治疗作用。这些发现表明口服大分子多糖如HCP可能通过直接调节肠肺轴Th17 / Treg细胞的平衡来减轻IAV感染小鼠的肺损伤。我们的结果提供了潜在的机制，多糖对肺部感染的治疗作用。这些发现表明口服大分子多糖如HCP可能通过直接调节肠肺轴Th17 / Treg细胞的平衡来减轻IAV感染小鼠的肺损伤。我们的结果提供了潜在的机制，多糖对肺部感染的治疗作用。