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Charcot-Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear.A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow-up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis.Thirty three (30.00%) patients developed recurrence during a 24-month postoperative follow-up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity.The crystalline CLC structures in nasal tissues may serve as an easy-counting and promising biomarker to predict CRSwNP recurrence.

Eosinophils play critical roles in the development of allergic rhinitis (AR) by releasing toxic substance. Interleukin-35 (IL-35), a newly identified anti-inflammatory cytokine, had potent inhibitive role for eosinophil infiltration in allergic disease. However, the direct effect of IL-35 on eosinophil was not clear.Twenty AR children and sixteen controls were recruited. The correlation between IL-35 protein expression and blood eosinophil counts and activation was analyzed. The effect of IL-35 on eosinophil apoptosis and adhesion was analyzed by flow cytometry. Transwell system was used for the migration assay. The eosinophil cationic protein (ECP) from supernatant of eosinophils after IL-35 stimulation was detected by enzyme-linked immunosorbent assay kits.The IL-35 protein levels were negatively correlated with eosinophil counts (p .01) and ECP concentration (p .01) in AR children. IL-35 promotes apoptosis and inhibits adhesion, migration, and activation of eosinophils. Moreover, the mRNA expression of IL-12 receptor β2 and glycoprotein 130 were significantly enhanced by eosinophils after IL-35 stimulation. The apoptosis induced by IL-35 was mediated by phosphoinositide 3-kinase (PI3K) pathway. IL-35 inhibits adhesion of eosinophils through extracellular regulated protein kinases (ERK) and PI3K pathways. The eosinophil chemotaxis and activation affected by IL-35 were mediated by PI3K and p38 mitogen-activated protein kinase (MAPK) pathways.Our results confirmed that IL-35 played inhibitive roles in apoptosis, adhesion, migration, and activation of eosinophils in AR, implying that IL-35 may be used as treatment target in future.

Osteopontin (OPN) can regulate Th2 inflammation in allergic rhinitis (AR). A recent study suggested that group II innate lymphoid cells (ILC2s) were very important for airway inflammation. But the role of OPN in ILC2s regulation is not explored.Purified ILC2s were stimulated by human recombinant OPN. The expression of GATA3 and RORα was assayed using real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay. MiR-181a was transfected into eosinophils to test the OPN production. The protein concentrations of interleukin (IL)-5 and IL-13 were examined using ELISA. Purified eosinophils and ILC2s were cocultured and stimulated by OPN and the activation of eosinophils was detected by ELISA.After OPN stimulation, the ILC2s proliferation, the mRNA levels of GATA3 and RORα, the protein of GATA3, RORα, IL-5 and IL-13 expression were up-regulated significantly in a dose dependent manner. Eosinophils cultured alone transfected with miR-181a mimics produced less OPN protein compared with eosinophils transfected with miR-control, whereas OPN production was significantly promoted when miR-181a inhibitor was transfected. In the eosinophils and ILC2s coculture system, eosinophil cationic protein (ECP) production induced by OPN or IL-33 were significantly higher than ECP production in eosinophils culture system. OPN presented similar potency with IL-33 in the activation of eosinophils. When anti-IL-5 antibody was added, the production of ECP was significantly inhibited.Our data for the first time provided new evidence that OPN played important roles in innate immunity of AR by regulation of ILC2s and the interaction between ILC2s and eosinophils.

Allergic rhinitis (AR) is a frequent inflammatory disorder of the upper respiratory tract, which has complex patterns of inheritance. Accumulating evidence has shown the key roles of DNA damage in inflammatory diseases, and the base excision repair (BER) is the primary pathway responsible for DNA repair during inflammation.Here, we performed a case-control study to investigate the associations between 20 potentially functional single nucleotide polymorphisms (SNPs) in 6 BER pathway genes (We found thatOur findings indicated that the genetic variants of

Background: The histopathology of pediatric chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is rarely reported due to low prevalence or the unavailability of tissue samples. Hence, we aimed to characterize and compare the histologic features and protein expression of Th1/Th2/Th17-related cytokines in pediatric CRSsNP and CRSwNP. Methods: The histologic characteristics of 15 children with CRSsNP, 52 children with CRSwNP, and 12 control participants were analyzed using hematoxylin and eosin staining. The expression of Th1/Th2/Th17-related cytokines were examined using immunohistochemistry and the enzyme-linked immunosorbent assay. Results: Pediatric subjects with CRSwNP had more intact epithelium and less submucosal mucous glands compared to those with CRSsNP. Tissue eosinophils were more prevalent in the younger CRSwNP group compared to the older CRSwNP or the CRSsNP groups. The protein concentrations of Th2 cytokines were significantly higher in the CRSwNP group than the CRSsNP group or the control group. Moreover, the protein concentrations of Th17 cytokines were significantly higher in the younger CRSwNP group than the older CRSwNP group or the CRSsNP and control groups. The protein concentrations of Th1 and Th17 cytokines were also significantly higher in the CRSsNP group than the control group. Compared with non-eosinophilic CRSwNP, eosinophilic CRSwNP presented with elevated protein concentrations of Th1 and Th17 cytokines. Conclusion: For the first time, we showed that pediatric CRSwNP presents as eosinophilic with Th2/Th17 inflammation, whereas CRSsNP presents as Th1/Th17 inflammation. Our study may provide a theoretical basis for the precise treatment of pediatric CRS in the future.