Yin Yao

Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes

The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.

Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps

Background: The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. Objective: We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. Methods: We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real‐time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio‐Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of I&egr;‐C&mgr; and I&egr;‐C&ggr; circle transcripts was detected by using seminested PCR. Results: Increased formation of eLTs with germinal center–like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, I&egr;‐C&mgr; transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. Conclusion: eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP.

Increased expression of TIPE2 in alternatively activated macrophages is associated with eosinophilic inflammation and disease severity in chronic rhinosinusitis with nasal polyps: TIPE2 in CRSwNP

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disorder characterized by exaggerated local immune responses. Tumor necrosis factor‐α–induced protein 8–like 2 (TIPE2) is a novel protein with potential immune modulating function. The expression and function of TIPE2 in human airway diseases are unclear.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy

Allergen-specific IL-4+ Tfh cells may contribute to allergen-specific IgE production and correlate with clinical efficacy of AIT in AR patients, which may be a promising therapeutic target and biomarker for AIT in AR.

IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps

Background: Although upregulated expression of local IgD has been reported in patients with chronic rhinosinusitis (CRS), its function is unclear. Objective: We sought to explore the expression and function of soluble IgD in patients with CRS, particularly CRS with nasal polyps. Methods: IgD levels in sinonasal mucosa were analyzed by using RT‐PCR and ELISA. Numbers and phenotypes of IgD+ cells were studied by means of immunohistochemistry, immunofluorescence, and flow cytometry. HMC‐1 cells, a human mast cell line, and mast cells purified from eosinophilic polyps were cultured alone or with naive B cells purified from peripheral blood. The antigen specificity of nasal IgD was investigated by using ELISA. Results: The mRNA expression of immunoglobulin heavy constant delta gene, numbers of IgD+ cells, and protein levels of secretory IgD in sinonasal mucosa were increased in patients with CRS with or without nasal polyps compared with control subjects. Numbers of IgD+ plasmablasts were increased in both eosinophilic and noneosinophilic polyps, whereas numbers of IgD+ mast cells were only increased in eosinophilic polyps. Cross‐linking IgD induced serum preincubated HMC‐1 cells and polyp mast cells to produce B‐cell activating factor, IL‐21, IL‐4, and IL‐13 and to promote IgM, IgG, IgA, and IgE production from B cells. In eosinophilic polyps expression of those B cell–stimulating factors in mast cells and close contact between mast cells and B cells were found. Moreover, positive correlations of total IgD levels with total IgE levels and eosinophilia and upregulation of specific IgD against house dust mites were discovered in eosinophilic polyps. Conclusion: IgD‐activated mast cells can facilitate IgE production and eosinophilic inflammation in patients with CRS with nasal polyps.

Deficiency in interleukin-10 production by M2 macrophages in eosinophilic chronic rhinosinusitis with nasal polyps: IL-10+ M2 macrophages in CRSwNP

M2 macrophages are characterized by high interleukin‐10 (IL‐10) expression and are critical for resolving inflammation. Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional relevance in CRSwNP remains poorly understood.

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

Host immunity (innate and adaptive immunity) plays essential roles in the pathogenesis of inflammatory upper airway diseases, including allergic rhinitis and chronic rhinosinusitis. Recently, the discovery of novel innate immune cells, particularly innate lymphoid cells, has renewed our view on the role of innate immunity in inflammatory upper airway diseases. Meanwhile, the identification of new subsets of T helper (Th) cells, including Th22, Th9 and follicular Th cells, and regulatory B cells in the adaptive immunity, has broadened our knowledge on the complex immune networks in inflammatory upper airway diseases. In this review, we focus on these newly identified innate and adaptive lymphocytes with their contributions to the immunological disturbance in allergic rhinitis and chronic rhinosinusitis. We further discuss the perspective for future research and potential clinical utility of regulating these novel lymphocytes for the treatment of allergic rhinitis and chronic rhinosinusitis.

Dendritic cells in inflammatory sinonasal diseases

Dendritic cells (DCs) are critical in linking the innate and adaptive immune responses, which have been implicated in the pathogenesis of many immune and inflammatory diseases as well as the development of tumours. The role of DCs in the pathophysiology of lung diseases has been widely studied. However, the phenotype, subset and function of DCs in upper airways under physiological or pathological conditions remain largely undefined. Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two important upper airway diseases with a high worldwide prevalence. Aberrant innate and adaptive immune responses have been considered to play an important role in the pathogenesis of AR and CRS. To this end, understanding the function of DCs in shaping the immune responses in sinonasal mucosa is critical in exploring the pathogenic mechanisms underlying AR and CRS as well as in developing novel therapeutic strategies. This review summarizes the phenotype, subset, function and regulation of DCs in sinonasal mucosa, particularly in the setting of AR and CRS. Furthermore, this review discusses the perspectives for future research and potential clinical utility focusing on DC pathways in the context of AR and CRS.