Immune-inflammatory endotypes of chronic rhinosinusitis: from epithelial alarmins to personalized therapy

Chronic rhinosinusitis (CRS) is a prevalent and complex inflammatory disease within otolaryngology, traditionally classified into phenotypes based on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. However, these phenotypic classifications inadequately capture the underlying pathophysiological heterogeneity of CRS. Recently, immune-inflammatory endotyping has emerged as a pivotal approach to better characterize CRS by delineating distinct inflammatory pathways, primarily type 1, type 2, and type 3 immune responses, each driven by unique immune cells and cytokine profiles. Epithelial-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25, alongside immune cells including group 2 innate lymphoid cells (ILC2), T helper 2 (Th2), and Th17 cells, play critical roles in modulating the immune landscape of CRS. Moreover, variations in immune responses among different populations highlight the disease's heterogeneity and underscore the need for precise immunological characterization. This review comprehensively summarizes recent advances in the immune-inflammatory endotyping of CRS, elucidates the underlying immunopathogenic mechanisms, and discusses the clinical significance of these endotypes. By integrating current research findings, this article aims to provide a theoretical foundation for the development of personalized therapeutic strategies tailored to distinct immune-inflammatory profiles in CRS patients.