xRead - Nasal Obstruction (September 2024) Full Articles

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International consensus statement on rhinosinusitis

X.C.12 Contributing Factors for CRSwNP: Innate Immunity The topic of innate immunity of the sinonasal cavity was introduced in Section IX.C.11. with regard to CRSsNP and there is some degree of overlap between studies particu larly with respect to the role of antimicrobial proteins and pattern recognition receptors. This section will highlight the most current data regarding innate immune cell and epithelial derived cytokine contributions in CRSwNP. Eosinophils. Twelve studies revealed that eosinophil counts in the nasal polyp tissue or nasal secretions of CRSwNP patients were remarkably higher than in controls. 818–821,824,1375,1459–1464 Three studies found that the numbers of peripheral blood eosinophils were significantly increased in CRSwNP or atopic CRSwNP patients com pared to healthy controls. 817,1462,1464 However, Zhang et al. 1465 found that tissue eosinophils in NP tissue from China, as measured by ECP and cytokine/chemokine lev els (IL-5 and eotaxin), were not significantly different from control tissue and were significantly lower in terms of numbers of eosinophils as compared with polyps from white subjects. Conversely, 3 studies found that the tissue eosinophils in Asian CRSwNP patients were significantly higher than that of controls. In the past 2 decades, the degree of eosinophilia in NPs appears to have increased in Asian patients. 1466–1468 Taken together, this large body of evidence demonstrated that the majority of patients with CRSwNP demonstrate eosinophillic inflammation. These results suggest that eosinophils play an important role in the pathogenesis of CRSwNP. Regardless of eth nicity and geographic region, eosinophilia in patients with CRSwNP strongly correlates with TH 2 immune response. Eosinophils were found to be express tissue factors that ini tiate the extrinsic coagulation cascade and subsequent fib rin deposition in the nasal mucosa. 1469 This altered coag ulation response may play a role in the formation of nasal polyp stroma. Neutrophils. Interestingly, 6 studies also showed that CRSwNP patients had significantly higher tissue neu trophils as compared to healthy controls. However, Zhang et al. 1465 found that no significant difference between CRSwNP and controls. Moreover, 2 studies revealed that the blood neutrophils counts were similar to that in the healthy subjects. 1462,1464 Macrophages. Limited evidence has shed light on the potential role of macrophages in the pathogenesis of CRSwNP. Van Zele et al. 821 reported no significant dif ference between CRSwNP and controls in terms of the number CD68 + macrophages. However, 2 studies form China showed that macrophages were significantly ele vated in the CRSwNP patients. 820,1470 Cao et al. 820 found

that CRSwNP patients have a significant number of macrophages as compared to healthy subjects. Yao et al. 1470 found that the number of CD68 + CD163 + alter natively activated (M2) macrophages were increased in eosinophilic CRSwNP. This study showed that TNF- α – induced protein 8–like 2 (TIPE2) was primarily expressed in M2 macrophages. 1470 Furthermore, M2 macrophages are the major FXIII-A–producing innate cells in NPs 1471 and increased FXIII-A levels by M2 macrophages might contribute to the evident excessive fibrin deposition. Mast cells. Two studies showed that mast cells are sig nificantly increased in NPs and primarily accumulate in the epithelium. 822,8231472 Type 2 cytokines, IL-5, IL-13, and IL-4, are secreted by mast cells, Th2 cells and group 2 ILCs 1473 and therefore mast cells may enhance Th2 inflammation. 1469 Basophils. Two studies 818,1462 revealed that there were no significant differences in the basophils of blood and nasal secretion between CRSwNP and controls however tissue basophils counts were remarkably elevated in the most of non-eosinophilic and some eosinophilic CRSwNP patients. The role of basophils in the pathogenesis of CRSwNP remains unclear. Fibroblasts. A larger body of evidence showed that the number of fibroblasts was significantly higher in CRSwNP as compared with controls. 825,826,1474,1475 Dobzansk et al. 1474 postulated that Wnt signaling by fibroblasts in CRSwNP may contribute to histological features of nasal polyps. Group 2 Innate Lymphoid Cells (ILCs). ILCs are recom bination activating gene (RAG)-independent innate cells and lack lineage markers for T cells or B cells. 1476 ILCs are divided into 3 genotypes. ILC2s can produce IL-13 and IL-5 when activated by the IL-33, IL-25, and TSLP. The latter cytokines can thereby induce eosinophilic airway inflammation. 1477 Mjösberg et al. 1478 reported that ILC2s are highly elevated in nasal polyp tissue of CRSwNP. This study indicated that ILC2s contribute to the process of eosinophilic inflammation in CRSwNP. Epithelial-Derived Innate Cytokines. Innate responses to aeroallergens and inflammatory stimuli can induce the epithelial-derive innate cytokines IL-33, IL-25, and TSLP, which activate the ILC2s to release Th2 cytokines without antigen presentation. 1469 These cytokines may contribute to the activation of TH 2 inflammation. Furthermore, P glycoprotein (P-gp) has been shown to be overexpressed in CRSwNP epithelium and directly promotes the secretion of these epithelial derived cytokines. 1479,1480 In summary, there is significant evidence for altered innate immune responses in CRSwNP relative to control patients (Tables X-12 and X-13). The degree to which this response represents an etiopathologic factor vs a secondary response to other upstream events remains a subject of continued research.