鼻息肉中2型固有淋巴细胞亚群的异质性及其临床相关性

Background: Chronic rhinosinusitis with nasal polyps is characterized by type 2 (T2) inflammation with elevated IL-5 and IL-13. Although group 2 innate lymphoid cells (ILC2s) drive T2 inflammation, their subset diversity and clinical relevance in nasal polyps (NPs) remain unclear. Objective: We investigated cellular sources of T2 cytokines, subset heterogeneity of ILC2s, and the relationship between ILC2 subsets and clinical severity in chronic rhinosinusitis with NPs. Methods: ILC2s and CD4+ T cells were isolated from NP tissue and analyzed for cytokine production. ILC2s from 6 NP and 4 peripheral blood samples underwent single-cell RNA sequencing. Differential gene expression, subset heterogeneity, and pseudotime trajectory analyses were performed. Flow cytometry validated ILC2 subsets and associations with clinical parameters. Results: Under ex vivo conditions, NP-derived ILC2s produced higher IL-5 and IL-13 levels than TH2 cells. NP-derived ILC2s showed downregulation of early developmental and trafficking genes (CD48, S1PR1) and upregulation of T2-associated cytokines (IL5, IL13), chemokines (XCL1, CXCL8), remodeling factors (AREG, TNFSF14), and METRNL. Four ILC2 subsets reflecting activation states were identified: migratory (tissue-homing with less activation), transitional (intermediate activation), inflammatory (high activation and T2 cytokines), and exhausted-like (expression of inhibitory receptors [eg, TIGIT]). The combined number of T2 cytokine-enriched subsets (transitional, inflammatory, and exhausted-like ILC2s) correlated with Lund-Mackay computed tomography scores. Inflammatory and exhausted-like ILC2s were associated with clinical symptom severity. Conclusion: ILC2s are one of the important effector populations driving local T2 inflammation in NPs and include 4 subsets with specific clinical associations. Subset-level ILC2 profiling may clarify chronic rhinosinusitis with NP pathophysiology and inform clinical stratification.