HHX-5, a derivative of sesquiterpene from Chinese agarwood, suppresses innate and adaptive immunity via inhibiting STAT signaling pathways

Abstract

Induction of excessive, prolonged, or dysregulated immune responses causes immunological disorders, such as inflammatory diseases, autoimmune diseases, allergic diseases, and organ-graft rejections. In the present study, we investigated the inhibitory effects of HHX-5, a derivative of sesquiterpene from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat above immunological disorders. The results showed that HHX-5 significantly inhibited the activation of macrophages and neutrophils which play important roles in innate immunity. Furthermore, HHX-5 strongly suppressed adaptive immunity via inhibiting differentiation of naive CD4⁺ T cells into Th1, Th2, and Th17 cells and suppressing activation, proliferation and differentiation of CD8⁺ T cells and B cells. The mechanism study showed that HHX-5 significantly inhibited STAT1 signaling pathway in macrophages and suppressed STAT1, STAT4, STAT5, and STAT6 signaling pathways in naive CD4⁺ T cells. In conclusion, we demonstrated that HHX-5 can strongly inhibit innate and adaptive immunity via suppressing STAT signaling pathways and has potential to be developed into therapeutic drug for treat immunological disorders.

Keywords: Adaptive immunity; HHX-5; Immunological disorder; Innate immunity; STAT signaling pathways; Sesquiterpene.