Abstract：
The dramatic changes in global climate on human health have been extremely severe. The immune disorder caused by low temperature and high humidity (LTHH) have become a severe public health issue. Clinically, Jingfang granule (JF) has the effect of dispelling cold and eliminating dampness, and is widely used in the treatment of cold caused by wind and cold, autoimmune diseases, and COVID-19 with cold-dampness stagnating in the lung pattern. Our study aims to elucidate the effect of JF on LTHH-induced immune disorders in mice as well as the underlying mechanisms. In this study, JF increased the spleen index, improved fecal character, repaired the intestinal barrier and alleviated intestinal inflammatory responses. Most importantly, JF ameliorated immune disorder in LTHH mice, which was manifested primarily by the significant increase in gdT, CD8+ Tcm, and CD8+ Tem cells, as well as the decrease in TH1, TH17, CD4+ Tem1, CD4+ Tem2, immature NK, mature NK cells, and M1-like macrophages. Interestingly, the JF treatment not only regulated the gut microbiota by decreasing the abundance of harmful bacteria, as well as up-regulating the abundance of beneficial bacteria, but also ameliorated the metabolic disorders by reversing the levels of fecal metabolites to normality. The results of the correlation analysis demonstrated a significant association among gut microbiota, fecal metabolites and immune cells. In addition, JF inhibited the TLR4/NF-κB/NLRP3 pathway in LTHH mice. In conclusion, our results suggested that JF alleviated inflammation and immune disorders in LTHH mice by restoring gut microbiota and fecal metabolism.
摘要：
全球气候的急剧变化对人类健康的影响极为严重。低温高湿（LTHH）引起的免疫紊乱已成为严重的公共卫生问题。临床上,井芳颗粒（JF）具有祛寒祛湿的作用，并广泛用于治疗由风和寒冷引起的寒冷，自身免疫性疾病，和COVID-19，寒湿停滞在肺部模式。我们的研究旨在阐明JF对LTHH诱导的小鼠免疫紊乱的影响以及潜在的机制。在这项研究中,JF增加了脾脏指数，改善粪便特性，修复肠道屏障,缓解肠道炎症反应。最重要的是,JF改善了LTHH小鼠的免疫紊乱，这主要表现为gdT的大幅增长，CD8+Tcm，和CD8+Tem细胞，以及TH1，TH17，CD4+Tem1，CD4+Tem2，未成熟NK，成熟的NK细胞，和M1样巨噬细胞。有趣的是,JF治疗不仅通过减少有害细菌的丰度来调节肠道微生物群，以及上调有益细菌的丰度，而且还通过将粪便代谢物的水平逆转至正常水平来改善代谢紊乱。相关性分析的结果表明肠道微生物群之间存在显着关联，粪便代谢产物和免疫细胞。此外,JF抑制LTHH小鼠TLR4/NF-κB/NLRP3通路。总之,我们的结果表明，JF通过恢复肠道菌群和粪便代谢来减轻LTHH小鼠的炎症和免疫紊乱。
