Background: Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored. Objectives: We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP). Methods: Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing. Results: Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1a, IL-1b, TNF-a, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis. Conclusions: Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS. (J Allergy Clin Immunol 2023;151:991-1004.)

Background: Although metabolomics provides novel insights into disease mechanisms and biomarkers, the metabolic alterations in local tissues affected by chronic rhinosinusitis (CRS) are unknown. Objective: This study aimed to determine the metabolomic profiles of sinonasal tissues associated with different types of CRS and their treatment outcomes. Methods: Untargeted metabolomic profiling was performed on sinonasal tissues obtained from patients with eosinophilic CRS with nasal polyps (CRSwNP), noneosinophilic CRSwNP or CRS without nasal polyps (CRSsNP), and controls. The messenger RNA (mRNA) levels of inflammatory cytokines in nasal tissues were detected by quantitative real-time reverse transcriptase PCR. Nasal polyp tissues were cultured ex vivo and treated with glutathione. Results: Distinct metabolomic profiles were observed for the CRS subtypes. Eosinophilic CRSwNP had profoundly enhanced unsaturated fatty acid oxidization, which correlated with mucosal eosinophil numbers and IL-5 mRNA levels. Noneosinophilic CRSwNP was characterized by uric acid accumulation. Increased uric acid levels were positively correlated with mucosal neutrophil numbers and IFN-gamma, IL-17A, IL-1 beta, and IL-8 mRNA levels. Disrupted purine metabolism was specifically detected in CRSsNP. Reduced levels of amino acid metabolites were found in eosinophilic CRSwNP and CRSsNP, and were inversely associated with mucosal total inflammatory cell numbers and inflammatory cytokines. Compared to non-difficult-to-treat CRS, difficult-to-treat CRS had higher glutathione disulfide levels, which were positively correlated with IL-8 mRNA levels. Glutathione treatment reduced IL-8 mRNA expression in cultured nasal polyp tissues. Conclusions: Specific metabolic signatures are associated with different types of CRS, inflammatory patterns, and disease outcomes, which may provide novel insights into pathophysiologic mechanisms, subtype-specific biomarkers, and treatment targets of CRS.

Background: Local immunoglobulin hyperproduction is observed in nasal polyps (NPs) with and without ectopic lymphoid tissues (eLTs). Objective: Our aim was to identify the T-cell subsets involved in local immunoglobulin production independent of eLTs in NPs. Methods: The localization, abundance, and phenotype of CD4(+) T-cell subsets were studied by immunofluorescence, flow cytometry, and single cell RNA sequencing. Purified nasal T-cell subsets were cultured with autologous peripheral naive B cells to explore their function. Programmed death ligand 1 and programmed death ligand 2 expression in NPs was investigated by immunofluorescence staining and flow cytometry. Results: Accumulation of PD-1(high) CXCR5(-)CD4(+) T cells outside lymphoid aggregates was found in NPs. Nasal PD-1(high) CXCR5(-)CD4(+) T cells were characterized by a unique phenotype that was related to B-cell help and tissue residency and distinct from PD-1(high)CXCR5(+) and CXCR5(+) CD4(+) T cells in NPs as well as PD-1(high) CXCR5(high) CD4(+) follicular helper T cells in tonsils. Compared with the frequencies of PD-1(high) CXCR5(-)CD4(+) T cells and their IFN-gamma(+), IL-17A(+), and IL-21(+) subsets in the control inferior turbinate tissues, the frequencies of these cells and their subsets were increased in both eosinophilic and noneosinophilic NPs, whereas the frequencies of the IL-4(+) and IL-4(+), IL-21(+) subsets were increased only in eosinophilic NPs. Nasal PD-1(high) CXCR5(-)CD4(+) T cells induced immunoglobulin production from B cells in a potency comparable to that induced by tonsillar follicular helper T cells. PD-1(high) CXCR5(-)CD4(+) T-cell frequencies were correlated with IgE levels in eosinophilic NPs. PD-L1 and PD-L2 suppressed the function of PD-1(high) CXCR5(-)CD4(+) T cells, and their levels were reduced in NPs. PD-1(high) CXCR5(-)CD4(+) T-cell abundance was associated with the postsurgical relapse of NPs. Conclusion: PD-1(high) CXCR5(-)CD4(+) T cells participate in local immunoglobulin production independent of eLTs in NPs.

Nasal polyps (NPs) are heterogeneous and occur in chronic rhinosinusitis, a complex disorder with high rates of postoperative recurrence.1 Identification of predictors for recurrence is useful for improved personalized and holistic disease management. To date, previous attempts to predict NP recurrence are limited by the invasive nature of surgical tissue sample acquisition and the small number of biomarkers analyzed, which have been mostly related to type 2 (T2) and eosinophilic inflammation.2,3 The predictive value of T2 biomarkers may be impaired by the heterogeneous feature of NPs, and other biomarkers such as neutrophils may be more effective in predicting prognosis in patients with noneosinophilic NPs.

Follicular helper T (T FH ) cells are a specialized subset of CD4 + T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of T FH cell survival remains unclear. Here we report that T FH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for T FH cell survival. The deletion of GPX4 in T cells selectively abrogated T FH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased T FH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium–GPX4–ferroptosis axis in regulating T FH homeostasis, which can be targeted to enhance T FH cell function in infection and following vaccination.

Purpose The pathogenic mechanisms of antrochoanal polyps (ACPs) remain largely unknown. This study aimed to characterize inflammatory patterns and tissue remodeling features in ACPs. Methods Inflammatory cell infiltration and tissue edema severity as well as fibrin deposition in ACPs and bilateral eosinophilic and noneosinophilic nasal polyps (NPs) were studied with immunohistochemical and immunofluorescence staining. Cytokine levels in sinonasal tissues were detected with the Bio-Plex assay. The expression of coagulation and fibrinolytic markers was measured using reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assays. Results Compared to control tissues and bilateral eosinophilic and noneosinophilic NPs, ACPs had higher levels of neutrophil infiltration and expression of myeloperoxidase (MPO), interleukin (IL)-8 and interferon (IFN)-γ. In total, 94.4% of ACPs demonstrated an eosinophil cationic protein/MPO ratio of < 1, compared to 79.0% of noneosinophilic and 26% of eosinophilic NPs. Principle component and multiple correspondence analyses revealed a neutrophilic and type 1 inflammation pattern in ACPs. Compared to control tissues, edema scores and fibrin deposition were increased, whereas d-dimer and tissue plasminogen activator (tPA) levels were decreased in ACPs and bilateral NPs, with more prominent changes in ACPs even than in eosinophilic NPs. The tPA levels were negatively correlated with IFN-γ, IL-8, and MPO levels in ACPs. Neutrophils were the major cellular source of IFN-γ in ACPs, and the number of IFN-γ+ neutrophils was elevated in ACPs than in control tissues and bilateral eosinophilic and noneosinophilic NPs. Conclusions ACPs are characterized by the neutrophilic and type 1 inflammation endotype. Neutrophil-derived IFN-γ is associated with reduced tPA production in ACPs.

BACKGROUND:Cold-inducible RNA-binding protein (CIRP) is a newly identified damage-associated molecular pattern molecule. Its roles beyond promoting inflammation and in human diseases are poorly understood. This study aimed to investigate the involvement of CIRP in chronic rhinosinusitis with nasal polyps (CRSwNP).METHODS:Immunohistochemistry, quantitative RT-PCR, and ELISA were used to detect the expression of CIRP and matrix metalloproteinases (MMPs) in sinonasal mucosal samples and nasal secretions. Human nasal epithelial cells (HNECs) and THP-1 cells, a human monocytic/macrophage cell line, were cultured to explore the regulation of CIRP expression and MMP expression.RESULTS:Cytoplasmic CIRP expression in nasal epithelial cells and CD68+ macrophages in sinonasal tissues, and CIRP levels in nasal secretions were significantly increased in both patients with eosinophilic and noneosinophilic CRSwNP as compared to those in control subjects. IL-4, IL-13, IL-10, IL-17A, TNF-α, Dermatophagoides pteronyssinus group 1, and lipopolysaccharide induced the production and secretion of CIRP from HNECs and macrophages differentiated from THP-1 cells. CIRP promoted MMP2, MMP7, MMP9, MMP12, and vascular endothelial growth factor A (VEGF-A) production from HNECs, macrophages differentiated from THP-1 cells, and polyp tissues, which was inhibited by the blocking antibody for Toll-like receptor 4, but not advanced glycation end products. The expression of MMPs and VEGF-A in tissues correlated with CIRP levels in nasal secretions in patients with CRSwNP.CONCLUSIONS:The upregulated production and release of CIRP from nasal epithelial cells and macrophages may contribute to the edema formation in both eosinophilic and noneosinophilic CRSwNP by inducing MMP and VEGF-A production from epithelial cells and macrophages.

Abstract Objective Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disorder characterized by heightened and sustained inflammation. A20 is a novel multifunctional protein with immunomodulatory effects. We sought to investigate the expression of A20 in sinonasal mucosa, and its association with local inflammation and disease severity in patients with CRSwNP. Methods The expression of A20 in sinonasal samples was assessed by quantitative RT-PCR, IHC, and Western blot. The numbers of local inflammatory cells were counted. CT scan findings and symptom severity were scored. Primary nasal epithelial cells were cultured to explore the regulation of A20 expression. Results Compared with control tissues and non-eosinophilic polyps, the mRNA and protein expression of A20 was significantly down-regulated in eosinophilic polyps. A20 was mainly expressed by epithelial cells. The expression of A20 in nasal epithelial cells was significantly reduced in eosinophilic polyps in comparison with those in non-eosinophilic polyps and control tissues. There was a further decrease in A20 expression in nasal epithelial cells in patients with eosinophilic polyps with asthma compared to those without asthma. A20 mRNA was induced by TNF-α, LPS, dsRNA, and dexamethasone, whereas was inhibited by IL-4 and IL-13 in human primary nasal epithelial cells. A20 mRNA levels in nasal epithelial cells negatively correlated with IL-4 and IL-13 levels and eosinophil numbers in sinonasal mucosa. Importantly, mRNA levels of A20 in nasal epithelial cells negatively correlated with disease duration and so on. Conclusions The decreased expression of A20 might contribute to eosinophilic inflammation and disease progression in patients with CRSwNP.

Background: The role of IL-37, an immunosuppressive cytokine, in patients with inflammatory diseases is unclear. Objective: We sought to explore the expression and pathogenic function of IL-37 in patients with chronic rhinosinusitis (CRS). Methods: Expression levels of IL-37, IL-18 receptor alpha, IL-1 receptor 8, Mex3 RNA binding family member B (Mex3B), and thymic stromal lymphopoietin (TSLP) in nasal samples were studied by using quantitative RT-PCR, immunohistochemistry, Western blotting, and ELISA. Human nasal epithelial cells (HNECs) and the BEAS-2B cell line were stimulated with various cytokines and Toll-like receptor (TLR) agonists. In some experiments BEAS-2B cells were transfected with Mex3B small interfering RNA or overexpressing lentiviruses. Genes regulated by IL-37b in HNECs were studied by using RNA sequencing analysis. IL-37b function was confirmed in mice in vivo. Results: Compared with control subjects, although mRNA and protein expression of IL-37 were upregulated in diseased tissues, especially in nasal epithelial cells, in patients with CRS without nasal polyps or in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), IL-37 levels in nasal secretions were reduced in patients with eosinophilic CRSwNP. Type 2 cytokines inhibited IL-37 secretion from HNECs. HNECs expressed IL-37 receptors, IL-18 receptor alpha, and IL-1 receptor 8. IL-37b downregulated the expression of Mex3B, a TLR3 coreceptor, in HNECs. IL-37b suppressed polyinosinic-polycytidylic acid- induced TSLP production in HNECs in vitro and in murine nasal epithelial cells in vivo. Knocking down or overexpressing Mex3B in BEAS-2B cells abolished the inhibitory effect of IL-37b. Secreted IL-37 levels negatively correlated with Mex3B and TSLP levels and eosinophil numbers in patients with eosinophilic CRSwNP. Conclusions: The suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with CRSwNP.

Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)-mediated hypersensitivity. Emerging evidence suggests that follicular helper T (TFH ) cells, rather than type 2 T-helper (TH 2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (TFR ) cells, a specialized subset of regulatory T (TREG ) cells resident in B-cell follicles, restricts TFH cell-mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long-lived, high-affinity plasma and memory B-cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5+ TFH cells, not CXCR5- conventional TH 2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5+ TFR cell deletion. Upregulation of TFH cell activities, including a skewing toward type 2 TFH (TFH 2) and IL-13 producing TFH (TFH 13) phenotypes, and defects in TFR cells have been identified in patients with allergic diseases. Allergen immunotherapy (AIT) reinstates the balance between TFH and TFR cells in patients with allergic diseases, resulting in clinical benefits. Collectively, further understanding of TFH and TFR cells and their role in the immunopathogenesis of allergic diseases creates opportunities to develop novel therapeutic approaches.

Nasal polyps (NPs) are benign edematous outgrowths of the sinonasal mucosa with excessive plasma protein accumulation in the lamina propria (LP).1,2 Recent studies indicate an important role of dysregulation of the coagulation and fibrinolytic cascade in edema formation and NP pathogenesis,3,4 which might be a promising target for the treatment of NPs.5 Takabayashi et al reported that type 2 cytokine–mediated downregulation of tissue plasminogen activator (tPA) might lead to enhanced fibrin deposition in LP and therefore result in edema development in NPs in white patients.

BACKGROUND:The contribution of B-cell subsets and T-B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This study aimed to outline circulating B-cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR.METHODS:IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigen-specific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co-cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B-cell subsets and clinical benefits of AIT were analyzed.RESULTS:Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19+ CD20+ CD27+ IgD- switched memory B cells was significantly enhanced and positively correlated with antigen-specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL-4, which was unable to be sufficiently suppressed by AR-associated Tfr cells with defective IL-10 expression. CD23 expression on switched memory B cells was downregulated after 12-month AIT, which positively associated with disease remission in AR patients.CONCLUSION:T-B cell interaction, bridged by CD23 expression particularly on switched memory B cells, may be involved in the disease pathogenesis and mechanism of AIT in patients with AR.

BACKGROUND:Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear.OBJECTIVE:To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs.METHODS:The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study.RESULTS:The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 β2 in NPs with eLTs. CXCL13 upregulated LTα1 β2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 β2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model.CONCLUSION:We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 β2 in the enlargement of eLTs in NPs.

BACKGROUND:The mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin-1 (HK-1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSwNP.METHODS:HK-1, NK1R, and C-C motif chemokine ligand 24 (CCL24) expression in nasal tissues (53 eosinophilic CRSwNP, 32 non-eosinophilic CRSwNP, and 33 controls) was investigated by quantitative reverse transcript polymerase chain reaction (RT-PCR) and immunofluorescence staining. THP-1, a human monocytic leukemia cell line, and eosinophilic polyp tissues were stimulated with HK-1. Cells, tissues, and culture supernatants were subsequently collected for detection of the production of various inflammatory cytokines and chemokines by quantitative RT-PCR and enzyme-linked immunoassay.RESULTS:HK-1 and NK1R mRNA and protein expression were upregulated in eosinophilic and non-eosinophilic nasal polyps compared with control tissues, with eosinophilic polyps demonstrating a higher upregulation compared with that of non-eosinophilic polyps. Eosinophils constituted the major source of HK-1, whereas macrophages were the predominant cell type exhibiting NK1R in eosinophilic polyps. HK-1 induced CCL24 production from macrophages differentiated from THP-1 cells; this was abolished by an NK1R antagonist. HK-1 also induced CCL24 production from ex vivo-cultured eosinophilic nasal polyps. CCL24 was expressed by macrophages in eosinophilic but not non-eosinophilic polyps. The expression level of HK-1 correlated with CCL24 expression and tissue eosinophilia in eosinophilic nasal polyps.CONCLUSION:Eosinophil-derived HK-1 induces CCL24 production from macrophages and therefore exaggerates eosinophilic inflammation in CRSwNP.

Background: The function of follicular regulatory T (T-FR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood. Objective: We sought to investigate the phenotype, function, and clinical relevance of T-FR cells in patients with allergic rhinitis (AR). Methods: The phenotype and frequency of tonsillar and circulating T-FR cells were characterized by using flow cytometry. T-FR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between T-FR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed. Results: T-FR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating T-FR cells in blood were phenotypically and numerically correlated with tonsillar T-FR cells, and a reduction of circulating T-FR cells but not total or CXCR5(-) regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating T-FR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating T-FR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating T-FR cells were improved, which positively associated with disease remission. Conclusion: Impairment in T-FR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective T-FR cell function. T-FR cells might serve as a potential biomarker to monitor clinical response to AIT.

Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation.We sought to elucidate the role of antigen-specific CD38+ B cells in AIT.An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT.A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Treg cells to TH17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT.Antigen-specific CD38+ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to TH17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

BACKGROUND: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. METHODS:M1 and M2 macrophages and IL-10 expression in sinonasal tissues were detected by double-immunofluorescence staining. THP-1 cells, a human monocytic leukemia cell line, were stimulated with various cytokines to study macrophage polarization and IL-10 expression. Polyp size, computed tomography (CT) scans, and symptom severity were scored. RESULTS:Compared with numbers in control tissues, the numbers of total CD68+ macrophages, interferon regulatory factor 5-positive and CD68+ M1 macrophages, and CD163+ CD68+ and CD206+ CD68+ M2 macrophages were increased in both eosinophilic and non-eosinophilic polyps. However, compared with non-eosinophilic polyps, eosinophilic polyps contained fewer M1 macrophages and more M2 macrophages. Consistent with this, the M1/M2 macrophage ratio was increased in non-eosinophilic polyps, whereas it decreased in eosinophilic polyps. Strikingly, the numbers of IL-10+ CD68+ macrophages and the percentage of IL-10+ CD68+ macrophages relative to the total number of macrophages were decreased in eosinophilic polyps, despite the upregulation of M2 macrophages in this type of polyp. The number of IL-10+ CD68+ M2 macrophages correlated negatively with total symptoms scores, polyp sizes, total CT scores, and the total number of inflammatory cells in patients with eosinophilic CRSwNP. Poly I:C downregulated IL-10 expression in M2 macrophages differentiated from THP-1 cells in vitro. CONCLUSION:Impaired IL-10 production by M2 macrophages may contribute to sustained inflammation in eosinophilic CRSwNP.vv.

BackgroundChronic 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.MethodsThe expression of TIPE2 in sinonasal mucosal samples was assessed by means of quantitative reverse transcript–polymerse chain reaction, immunohistochemistry, and Western blotting. The human monocytic/macrophage cell line, THP‐1 cells, was stimulated with various cytokines. Computed tomography (CT) scan images, endoscopic findings, and symptoms were scored.ResultsCompared with non‐eosinophilic polyps and control mucosa, the mRNA and protein expression of TIPE2 was significantly upregulated in eosinophilic polyps, with a further increase in those with asthma. The number of CD68+CD163+ alternatively activated (M2) macrophages was increased in eosinophilic polyps. TIPE2 was mainly expressed by M2 macrophages in sinonasal mucosa and its expression was upregulated in M2 macrophages in eosinophilic polyps. Interleukin (IL)‐4 and IL‐13, but not interferon (IFN)‐γ or IL‐17A, induced TIPE2 expression in differentiated THP‐1 cells. The mRNA levels of IL‐4 and IL‐13 correlated with the mRNA levels of TIPE2 and M2 macrophage markers in sinonasal mucosa. Importantly, the number of TIPE2+ cells, particularly TIPE2+CD163+CD68+ M2 macrophages, correlated positively with the number of eosinophils and total inflammatory cells in sinonasal mucosa, as well as disease duration, CT scores, hyposmia scores, and polyp size in CRSwNP.ConclusionThe T‐helper 2 milieu is able to induce TIPE2 expression in macrophages. TIPE2‐positive M2 macrophages potentially contribute to eosinophilic inflammation and disease progression in CRSwNP.

Objective To study the diagnosis and treatment of omental torsion.Methods 73 patients with omental torsion from Jan 1995 to Dec 2009 in literatures together with the one we reported were reviewed and analyzed The range of ages was from 3 to 65 years,and the median age was 25.3 years.Among them,35 cases were less than 18 years old(47%,and 27 with obesity) and others more than 18 years old(53%,1 with obesity).The accurate diagnosis before operation exsited in 9 patients.49 patients(66%) were diagnosed as primary omental torsion,and childhood obesity was the most related factor.Conversely,25(34%) were diagnosed as secondary omental torsion,while the most common reason was adhersion.In contrast with other clinical symotoms and signs,abdominal pain and tenderness were occurred in almost every people.Bultro sonography(positive rate:24%,6/25) was hardly useful in diagnosis but CT (positive rate:96%,23/24) and MRI(positive rate:100%,2/2) were beniticial.Operation was applied in all patients,while laparoscopy was uesed in 23 patients.As a rule,the appendix was removed together in 61 persons.The cobort of patients was recoverd fully without serious complications such as hemorrhage and intestinal infarction.Conclusion Omental torsion was a relatively rare disease,and the diagnosis should be easy with the help of CT and MRI,and the laparoscopy was the better choice for surgeons.