Interleukin-31 in Respiratory Type 2 Inflammatory Diseases: Mechanistic Insights and Therapeutic Potential

Shuang Yao,1,2,* Yan Zhao,1,2,* Zhimeng Li,3,4 Hongfei Lou,5,* Luo Zhang1,2,4,6,* 1Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission and Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing Institute of Otolaryngology, Beijing, People’s Republic of China; 3Department of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing, People’s Republic of China; 4Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 6Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfei Lou, Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 3 Fenyang Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email [email protected] Luo Zhang, Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 1, Dongjiaominxiang St, Dongcheng District, Beijing, 100730, People’s Republic of China, Email [email protected]: Respiratory type 2 inflammatory diseases, including asthma and allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP), are characterized by epithelial dysfunction, immune dysregulation, and chronic airway inflammation. Interleukin-31 (IL-31), primarily produced by Th2 cells and other immune and structural cells, has emerged as a pivotal mediator in these conditions. By activating the JAK/STAT and MAPK signaling, IL-31 drives chemokine release, eosinophil recruitment, mucus hypersecretion, and neuroimmune responses. Clinical studies demonstrate that IL-31 levels are elevated and correlate with disease severity, positioning IL-31 as a promising biomarker for diagnosis, prognosis, and treatment response monitoring. Importantly, IL-31 uniquely links type 2 inflammation with sensory nerve dysfunction, addressing unmet clinical needs not fully resolved by conventional IL-4/IL-5–targeted therapies. In this review, we synthesize current mechanistic and clinical evidence on IL-31 in asthma, AR, and CRSwNP, highlight its distinct value compared with other cytokines, and outline the major challenges and research questions that remain unanswered. We further discuss potential translational strategies, including biomarker development and IL-31–targeted interventions, which may provide new opportunities for precision medicine in respiratory type 2 inflammatory diseases.Keywords: IL-31, respiratory inflammatory diseases, T type 2 cells, mechanism of action, therapeutic targets