Zhi-Chao Wang

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.

Interferon-γ-induced insufficient autophagy contributes to p62-dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps

Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP).

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.

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

OBJECTIVE Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on transcription factor expression and cytokine production patterns in different innate lymphoid cell (ILC) types, in parallel with those of adaptive CD4+ T-helper (TH) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging for the immune response deviation into type 1 (orchestrated by ILC1s and Tc1, and TH1 cells), type 2 (characterized by ILC2s and Tc2 and TH2 cells), and type 3 (mediated by ILC3s and Tc17 and TH17 cells). In addition, cluster analysis has been applied to endotyping of CRS in recent years, which has provided additional novel insights into CRS pathogenesis. This review assessed pathologic mechanisms of CRS based on type 1, 2, and 3 immune responses and how they inform us to begin to understand CRS endotypes. This review also assessed recent cluster analysis studies of CRS endotypes. The impact of endotype on therapeutic management of CRS also is summarized. DATA SOURCES Review of published literature. STUDY SELECTIONS Relevant literature concerning CRS endotypes and possible underlying mechanisms was obtained from a PubMed search and summarized. RESULTS AND CONCLUSION CRS with and without nasal polyps are composed of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the best-studied endotype and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.