IL-17-Related Pathways and Myeloid Cell Function are Involved in the Mechanism of Sublingual Immunotherapy with Artemisia annua for Seasonal Allergic Rhinitis.

Abstract

The mechanisms underlying immune tolerance induction during sublingual immunotherapy (SLIT) of seasonal allergic rhinitis (SAR) remain insufficiently understood. This study aimed to investigate the molecular and immunological process involved in SLIT. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to examine the functions of differentially expressed genes (DEGs) in leukocytes from 11 SAR patients at three time points: baseline, peak pollen phase (PPP), and end-of-treatment. Patients received a 4-month SLIT course with Artemisia annua (A. annua) extract (n = 5) or placebo (n = 6). Plasma cytokine levels were measured in a validation cohort of 15 SAR patients (9 in the SLIT group and 6 in the placebo group) using Luminex assays. The results showed that A. annua SLIT inhibited the upregulation of IL-17A-associated pathways and the expression of inflammatory mediators, including CXCL1, CCL7, and PLPP3, while enhancing myeloid immune cell function by increasing the expression of CD36, TYROBP, FCGR1A, and FCER1G. Additionally, A. annua SLIT reactivated myeloid immune cell-associated genes that were downregulated during PPP and significantly reduced IL-17A and GRO-β levels in plasma, compared to the placebo group. These findings suggest that A. annua SLIT alleviates SAR by modulating IL-17A pathways, reducing inflammatory responses, and enhancing myeloid immune cell function.