A genetic variant near TSLP is associated with chronic rhinosinusitis with nasal polyps and aspirin-exacerbated respiratory disease in Japanese populations

Dear Editor, Chronic rhinosinusitis with nasal polyps (CRSwNP), is a heterogenous disease associated with asthma, high degrees of disease severity, and a poor quality of life. Some patients with CRSwNP have a specific condition called aspirin-exacerbated respiratory disease (AERD) which is characterized by a triad of symptoms including CRSwNP, asthma, and sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). Genome-wide association studies (GWASs) have found significant associations between the thymic stromal lymphopoietin (TSLP) locus and asthma, allergic rhinitis, eosinophilic esophagitis, and nasal polyps (Supplementary Table 1). TSLP is produced by barrier epithelial cells and plays a central role in activating type 2-related inflammatory cells including TH2 lymphocytes, type 2 innate lymphoid cells, eosinophils, basophils, and mast cells. A recent study examined the presence of TSLP, IL-25 and IL-33 in nasal polyps from patients with CRSwNP and AERD and found significant elevations of TSLP mRNA in nasal polyps from CRSwNP and AERD compared to controls. Another study has shown that TSLP activates eosinophils and induces the expression of mast cell-derived PGD2 via mast cells, which plays a crucial role in the pathophysiology of AERD.