Regulating the balance of Th17/Treg cells in gut-lung axis contributed to the therapeutic effect of Houttuynia cordata polysaccharides on H1N1-induced acute lung injury

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.