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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory condition characterized by persistent sinus inflammation and tissue remodeling. Epithelial-derived alarmins, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), are critical mediators that initiate and amplify immune responses in CRSwNP. These alarmins are secreted by stressed or damaged nasal epithelial cells in response to environmental insults, such as allergens, microbial infections, pollutants, and proteases. Once released, they orchestrate immune cell activation and amplify inflammatory pathways. Targeting epithelial-derived alarmins has emerged as a promising therapeutic strategy for CRSwNP, with several biologics, including TSLP and IL-33 inhibitors, showing encouraging clinical outcomes. This review focuses on the role of epithelial-derived alarmins in CRSwNP, examining their expression patterns, regulatory mechanisms, and contributions to inflammation, evaluating the current progress in alarmin-targeted therapies, and exploring future research directions to optimize their clinical application.
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http://dx.doi.org/10.1007/s12016-025-09073-y | DOI Listing |
Clin Rev Allergy Immunol
June 2025
High Altitude Rhinology Research Center, Eye & ENT Hospital of Fudan University and People's Hospital of Shigatse City, Shanghai, Shigatse, China.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory condition characterized by persistent sinus inflammation and tissue remodeling. Epithelial-derived alarmins, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), are critical mediators that initiate and amplify immune responses in CRSwNP. These alarmins are secreted by stressed or damaged nasal epithelial cells in response to environmental insults, such as allergens, microbial infections, pollutants, and proteases.
View Article and Find Full Text PDFCurr Opin Allergy Clin Immunol
August 2025
Department of Translational Medical Sciences.
Purpose Of Review: Asthma is a heterogeneous disease encompassing distinct phenotypes and endotypes. Advances in elucidating the pathogenic role of type 2 (T2) cytokines and epithelial-derived alarmins have profoundly reshaped our understanding of airway inflammation in asthma. This review provides an updated perspective on how these mediators contribute to asthma pathobiology and examines their integration into emerging precision medicine strategies.
View Article and Find Full Text PDFChin Med
May 2025
Shanghai Research Institute of Acupuncture and Meridian,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background: Allergic asthma features Th2-mediated airway inflammation, with dendritic cells (DCs) playing a crucial role. Acupuncture shows promise in modulating immune responses, yet its mechanisms in allergic asthma are not well understood. This study explores how acupuncture alleviates Th2 airway inflammation by modulating lung CD11b DCs.
View Article and Find Full Text PDFLakartidningen
May 2025
postdoktoral forskare, Klinisk lung- och allergiforskning, institutionen för medicin Huddinge, Karolinska institutet.
Type 2 (T2) high asthma, characterized by T2 markers such as eosinophilia, is driven by type 2 innate lymphoid cells (ILC2) and allergen-activated T helper (Th2) cells. Epithelial-derived cytokines called alarmins, IL-33, TSLP, IL-25 and TL1A, acting on dendritic cells and ILC2, are key in driving both allergic and non-allergic T2 high asthma. Alarmins are produced in response to allergens, pathogens, pollutants etc.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
May 2025
Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy.
Background: IL-33 is an epithelial-derived alarmin with various roles in cancer. In melanoma, endogenous and exogenous IL-33 exert anti-tumor effects through the stimulation of several immune effector cells. In this study, we explored the combination of IL- 33 with Decitabine (DAC), a DNA methylation inhibitor that promotes immune recognition by re-activating silenced genes, for melanoma treatment.
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