Search

Background: Allergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. Methods: This retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months–1 year), the 2 years group (1–2 years), and the 3 years group (2–3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. Results: The total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. Conclusion: Our results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Background: 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. Methods: Here, we performed a case-control study to investigate the associations between 20 potentially functional single nucleotide polymorphisms (SNPs) in 6 BER pathway genes (PARP1, hOGG1, FEN1, APEX1, LIG3, and XRCC1) and AR susceptibility in 508 AR cases and 526 controls which originated in China. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for evaluating the association strength. Results: We found that hOGG1 rs1052133 G > C and XRCC1 rs2682585 G > A polymorphisms were associated with decreased AR risk (adjusted OR = 0.67, 95% CI = 0.47–0.94, P = 0.022; and adjusted OR = 0.21, 95% CI = 0.06–0.79, P = 0.022, respectively). Stratification analysis suggested that: hOGG1 rs1052133 GC/CC genotype reduced AR risk in subjects among following subgroups: age ≤60 months, females, and moderate AR; XRCC1 rs2682585 GG genotype decreased AR risk in subjects age >60 months, and LIG3 rs1052536 TT genotype increased AR risk in subjects of severe AR. Conclusion: Our findings indicated that the genetic variants of hOGG1, XRCC1, and LIG3 genes might affect AR susceptibility in the Chinese population, which will provide novel insight into the genetic underpinnings of AR from the DNA damage level.

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.

Background: Studies have shown that the number and function of type II innate lymphoid cells (ILC2) in peripheral blood of allergic rhinitis (AR) children increased significantly. This study aims to evaluate the role of miR-375 in the regulation of the differentiation and function of ILC2 through both in vivo and in vitro studies. Methods: The expression of miR-375, thymic stromal lymphopoietin (TSLP) and the frequency of ILC2 were detected and compared between AR children and controls by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbnent assay (ELISA) and flow cytometry, respectively. The miR-375 mimics or inhibitors were transfected into human nasal epithelial cells (HNECs), and the production of TSLP was detected by ELISA. HNECs and ILC2s were co-cultured to explore the role of miR-375 on ILC2s. AR mice models were established to prove the effect of miR-375 on ILC2s in vivo. Results: The expression of TSLP, miR-375, and the frequency of ILC2 were significantly higher in AR compared with controls. We found that the TSLP expression by HNECs were significantly higher when transfected with miR-375 mimics than in those transfected with miR-control and miR-375 inhibitor. In the coculture system, HNECs transfected with miR-375 mimics promote the type II cytokines production by ILC2, and this effect was blocked by anti-TSLP. Our results also showed that the miR-375 inhibitors attenuate allergic symptoms and production of type II cytokines in AR mice. Conclusions: Our findings suggest that miR-375-mediated regulation of ILC2 cells through TSLP, providing new potential treatment target for AR.