Immunopathology of Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is driven by a complex interplay between epithelial barrier dysfunction, innate immune activation and skewed adaptive responses. Disruption of the sinonasal epithelial surface permits entry of allergens, microbes and irritants, leading to release of alarmins such as interleukin-25, interleukin-33 and thymic stromal lymphopoietin. These cytokines instruct group 2 innate lymphoid cells (ILC2) and T helper 2 (Th2) lymphocytes to secrete type 2 cytokines including interleukin-4, interleukin-5 and interleukin-13. The resulting eosinophil recruitment, goblet cell hyperplasia and tissue remodelling underlie polyp formation. Concurrently, oxidative stress arising from excessive reactive oxygen species and impaired antioxidant defence contributes to persistent inflammation. Heterogeneity is evident in phenotypic endotypes, with eosinophilic and non-eosinophilic variants defined by differential cell infiltrates and cytokine profiles. Advances in molecular phenotyping have revealed the contribution of Th17 and regulatory T cells, as well as altered microbiome communities, to disease persistence. Recognition of these pathways has underpinned targeted therapies, including biologic agents against key cytokines and emerging antioxidant strategies aimed at restoring mucosal homeostasis.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Immunopathology of Chronic Rhinosinusitis with Nasal Polyps publication trend

The graph below shows the total number of articles in immunopathology of chronic rhinosinusitis with nasal polyps across all publications each year (not limited to Nature Index journals).

Technical terms

Type 2 inflammation (T2): An immune response dominated by Th2 cells and ILC2 releasing IL-4, IL-5 and IL-13, driving eosinophilic inflammation and IgE production.

Alarmins: Epithelial-derived cytokines (eg IL-25, IL-33, TSLP) that activate innate and adaptive type 2 immune pathways.

KEAP1–NRF2–HO-1 pathway: A cellular antioxidant signalling cascade that regulates expression of detoxifying enzymes to counteract oxidative stress.

Innate lymphoid cells (ILC2): Tissue-resident innate cells that rapidly produce type 2 cytokines in response to alarmins, contributing to early inflammatory responses.

Oxidative stress: A state of imbalance between pro-oxidant species (eg reactive oxygen species) and the antioxidant defence system, leading to tissue injury and sustained inflammation.

References

1. Chronic rhinosinusitis pathogenesis. Journal of Allergy and Clinical Immunology (2015).
2. IL-25/IL-33–responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa. Journal of Allergy and Clinical Immunology (2015).
3. Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps. Immunity Inflammation and Disease (2017).
4. Oxidative Stress and Antioxidants in Chronic Rhinosinusitis with Nasal Polyps. Antioxidants (2023).
5. The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. Frontiers in Immunology (2024).
6. Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction. Journal of Translational Medicine (2020).
7. Altered Th17/Treg Ratio in Nasal Polyps With Distinct Cytokine Profile. Medicine (2016).