Activated group 2 innate lymphoid cells (ILC2s) are important effector cells of Th2-type innate immune responses in eosinophilic airway inflammation by producing large amounts of Th2 cytokines such as IL-5, IL-13 and IL-4. Arachidonic acid metabolites including prostaglandins (PGs) and leukotrienes (LTs) play a vital role in homeostasis and inflammation. PGD2, LTB4, LTC4, LTD4, and LTE4 stimulate human ILC2s to produce Th2 cytokines. On the other hands, PGE2, PGI2 and lipoxin A4 inhibit Th2 cytokine productions from human ILC2s. Increasing evidences suggest that ILC2s are tissue-resident cells and their function and phenotype are influenced by the local microenvironment. Therefore, arachidonic acid metabolites in local mucosal tissues play very important roles in eosinophilic inflammation through tissue-resident ILC2s. ILC2s exist in both nasal polyp tissues in eosinophlic chronic rhinosinusitis (ECRS) and inferior nasal turbinate tissues in house dust mite (HDM)-induced allergic rhinitis. This review summarizes the association of tissue-resident ILC2s and arachidonic acid metabolites in nasal mucosa of ECRS and HDM-induced allergic rhinitis.
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by eosinophilic nasal polyposis. Because several types of cells play a role in pathogenesis, ECRS is a heterogenous disease. To identify each cell function is important for the individualization of therapy. The eosinophil is a granulocyte that contain eosinophil granule proteins (EGPs). EGPs have antiparasitic activity, on the other hand, closely related allergic inflammation due to its cytotoxicity. Eosinophil-derived neurotoxin (EDN) is one of the eosinophil granule proteins. In this study, we evaluated the function of EDN in ECRS pathogenesis. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases and were positively correlated with clinical disease activity. EDN expressed in the eosinophils of ECRS nasal polyps. Human nasal epithelial cells (HNEpCs) were stimulated with EDN, and the resultant changes in gene expression were detected by RNA sequencing. Pathway analysis revealed that the major canonical pathway affected by EDN stimulation was “regulation of the epithelial–mesenchymal transition (EMT) pathway”; the only gene in this pathway to be up-regulated was matrix metalloproteinase 9 (MMP-9). EDN may be involved in the pathogenesis of ECRS and also be an important therapeutic target.