Emu-miR-10a-5p in Echinococcus multilocularis-Derived-Extracellular Vesicles Alleviates Airway Inflammation in Mice with Allergic Asthma by Inhibiting Macrophage M2a Polarization Through LIF-Mediated JAK1-STAT3 Signaling

Yunzhuo Xin^1,2Rou Wen¹Dong Song³Jing Xiao⁴Xiaoping Gao³Mei Yin⁵Yanli Bai²Jie Wang^1*Xiangyu Zhou^6*Jiaqing Zhao^1*

• ¹Ningxia Medical University, Yinchuan, China
• ²Xi'an International Medical Center Hospital, Xi’an, China
• ³Department of Otolaryngology and Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, Henan Province, China
• ⁴Shiyan Integrated Traditional and Western Medicine Hospital, Shiyan, China
• ⁵Department of Respiratory Medicine, General Hospital of Ningxia Medical University,, Yinchuan, Henan Province, China
• ⁶Shizuishan First People's Hospital, Shizuishan, Ningxia, China

Parasites and parasite-derived extracellular vesicles (EVs) and microRNAs (miRNAs) can protect against inflammatory diseases, such as asthma. M2a macrophages facilitate the development of allergic asthma. miR-10a-5p is closely associated with asthma, and emu-miR-10a-5p (encapsulated in Echinococcus multilocularis EVs), shares seed-site sequences with mature human and mouse miRNAs. Here, we observed that E. multilocularis-derived EVs and their encapsulated emu-miR-10a-5p transcripts inhibited macrophage M2a polarization. We also found that emu-miR-10a-5p targeted leukemia inhibitory factor (LIF) mRNA and inhibited the downstream Janus kinase 1 (JAK1)-signal transducer and activator of transcription 3 (STAT3)-signaling pathway. We established a mouse model of ovalbumin (OVA)-induced allergic asthma and found that emu-miR-10a-5p alleviated pulmonary inflammation in mice with allergic asthma while inhibiting the accumulation of pulmonary M2a macrophages. emu-miR-10a-5p intervention inhibited LIF and JAK1-STAT3 signaling in the lungs of mice with allergic asthma. These findings suggest that emu-miR-10a-5p encapsulated in E. multilocularis EVs might regulate M2a macrophage polarization via the JAK1-STAT3 pathway by targeting and binding LIF in a cross-species manner, thereby alleviating airway inflammation in mice with allergic asthma. These findings enhance the current understanding of the mechanisms underlying immune regulation during infection and the maintenance of immune stability.