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Updated: Apr 11, 2026
Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
Published on: May 10, 2022
Heterogeneity and clinical relevance of group 2 innate lymphoid cells subsets in nasal polyps
Masanori Kidoguchi1, Naruhito Iwasaki2, Julie A Poposki2
1Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Otorhinolaryngology and Head & Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan; Center for Human Immunobiology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
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.
