Triptolide alleviates allergic airway inflammation by inhibiting group 2 innate lymphoid cell function

• Triptolide ameliorates type 2 immune responses in papain and IL-33 induced allergic airway inflammation. • In allergic airway inflammation, Triptolide modulates type 2 cytokine production by ILC2s. • ILC2-regulated genes are changed after Triptolide treatment such as Adrb2, Nmur1, tnfsf11, IL-5, IL-13, IL-9 and so on. • Triptolide has preventive and therapeutic effects on allergic airway inflammation. Group 2 innate lymphoid cells (ILC2s) produce the type 2 cytokines IL-5 and IL-13 and contribute to type 2 immune responses, such as allergic airway inflammation. However, specific drugs, especially traditional Chinese medicines, that target lung ILC2s have rarely been reported. Here, we demonstrate that triptolide ameliorates allergic airway inflammation by suppressing ILC2 activation. IL-33, which is produced mainly by epithelial cells, is the most powerful cytokine for activating ILC2s. Triptolide-treated ILC2s were found to be functionally impaired in response to interleukin (IL)–33 challenge. RNA-seq analysis revealed that triptolide impaired ILC2 function through inflammation-related signalling pathways. ILC2-related genes were up- and down-regulated under the treatment with TPL such as Adrb2, Nmur1, tnfsf11, IL-5, IL-13, IL-9 and so on. Interestingly, we observed not only preventive but also therapeutic effects of triptolide on allergic airway inflammation, indicating that triptolide may serve as a promising traditional Chinese medicine for the treatment of allergic airway inflammation by targeting ILC2s.