Tanshinone IIA ameliorates septic immunosuppression by balancing the Th17/Treg cell ratio and modulating Treg function after induction of autophagy.

Sepsis is a systemic inflammatory response syndrome due to infection with a high incidence and high mortality. The Tanshinone IIA (TSN) is an active ingredient extracted from the traditional Chinese medicine Danshen. This work attempted to investigate the functional role of TSN is sepsis. It was found that the ratio of Th17/Treg was increased in sepsis patients and mouse model. TSN reduced the ratio of Th17/Treg and the levels of IL-17, IL-23, TGF-β1, and IL-10 in CD4+ T cells. Proliferation of CD4+CD25-Teff cells was inhibited by TSN. The expression of co-stimulatory molecules ICOS and CTLA-4 was decreased in CD4+ cells following TSN treatment. Additionally, TSN elevated LC3-II/I expression and down-regulated p62, p-mTOR and p-p70S6K to activate autophagy. Autophagy activator rapamycin (Rapa) activated autophagy to reduce the ratio of Th17/Treg in CD4+ T cells. Autophagy inhibitor (3-MA) in activated autophagy to elevate the ratio of Th17/Treg in CD4+ T cells, which was abolished by TSN treatment. TSN alleviated the damage of kidney, lung and liver tissues and inhibited the ratio of Th17/Treg in sepsis mice by activating autophagy. In summary, this work demonstrated that TSN ameliorates sepsis-associated immunosuppression by activating autophagy and balancing the Th17/Treg cell ratio.