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Background and Aims: Epithelial barrier dysfunction plays a critical role in the initiation of a number of immune diseases; the causative factors are not fully understood. The present study aimed to elucidate the mechanism by which the eosinophil-derived interferon (IFN)-lambda induced the gut epithelial barrier dysfunction., Methods: The duodenal biopsies were obtained from patients with or without food allergies. The eosinophils and IFNλ expression were observed by immune staining. Intestinal epithelial cell line, T84 cells, and a mouse model were employed to observe the effect of IFNλ on the epithelial barrier function and the initiation of skewed T helper (Th)2 polarization in the mouse intestine., Results: IFNλ expression was observed in over 80% human eosinophils of the subjects with or without food allergies. Exposure to microbial products, lipopolysaccharide or peptidoglycan, could induce eosinophils to release IFNλ. Exposure to IFNλ could induce intestinal epithelial barrier dysfunction via inducing the epithelial cell apoptosis. Concurrent exposure to microbial products and food antigens could induce aberrant antigen specific Th2 polarization and Th2 pattern inflammation in the intestine., Conclusions: Eosinophils express IFNλ that can induce intestinal epithelial barrier dysfunction and promotes the initiation of the aberrant Th2 polarization in the intestine., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

It was reported that the expression of Toll‐like receptor (TLR) 9 may be related to Th2‐type allergic inflammation including allergic rhinitis (AR). However, little is known about the expression of TLR9 in the basophils in AR. In the present study, the expression of TLR9 was examined by flow cytometry analysis, and the expression of TLR9 mRNA in KU812 was determined by quantitative real‐time PCR. The results showed that the percentage of TLR9+CCR3+ cells in blood granulocytes increased by 46% in patients with AR, but not in peripheral blood mononuclear cells (PBMCs). Allergens namely Dermatophagoide allergen extract (DAE) and Platanus pollen allergen extract (PPAE) upregulated the expression of TLR9 in CCR3+ granulocytes by 76% and 84%, respectively. DAE and PPAE also enhanced the proportions of TLR9+CD123+HLA‐DR− cells and TLR9+CCR3+CD123+HLA‐DR− cells in granulocytes and PBMCs of patients with AR. In order to investigate the actions of allergens on basophils, KU812 cells were used. It was observed that all KU812 cells expressed TLR9, and the expression intensity of TLR9 in a single KU812 cell was elevated by CpG. IL‐37, IL‐31, IL‐33, Artemisia sieversiana wild allergen extract (ASWAE), DAE, OVA and Der p 1 induced an increase in the expression of TLR9 mRNA and IL‐6 production in KU812 cells. It was shown that the percentage of TLR9‐expressing basophils increased in the blood of ovalbumin (OVA)‐sensitized mice. In conclusion, an increased expression of TLR9 and the production of IL‐6 in basophils implicate that the contribution of basophils to AR is likely via TLR9. [ABSTRACT FROM AUTHOR]

Background: Large numbers of CD8+ T cells were observed in atopic dermatitis (AD) skin, and monocytes from AD patients showed increased prostaglandin E2 production. However, little is known about the expression of substance P (SP) and its receptor NK1R in blood leukocytes of patients with AD.Objective: To explore the expression of SP and NK1R in leukocytes of AD and the influence of allergens on SP and NK1R expression.Methods: The expression levels of SP and NK1R in patients with AD were examined by flow cytometry, ELISA and a mouse AD model.Results: The plasma SP level was 4.9-fold higher in patients with AD than in HC subjects. Both the percentage of SP expression in the population and mean fluorescence intensity (MFI) of SP expression were elevated in CD8+ T cells in the blood of AD patients. However, both the CD14+NK1R+ population and MFI of NK1R expression on CD14+ cells were enhanced in the blood of AD patients. Allergens ASWE, HDME and PPE failed to up-regulate SP expression in CD8+ T cells. However, allergens ASWE and HDME both enhanced NK1R expression on CD14+ blood leukocytes regardless of AD or HC subjects. OVA-sensitized AD mice showed an elevated proportion and MFI of SP-expressing CD8+ T cells in the blood, which agrees with the SP expression situation in human AD blood. Injection of SP into mouse skin did not up-regulate NK1R expression on monocytes.Conclusions: An elevated plasma SP level, up-regulated expression of SP and NK1R indicate that the SP/NK1R complex is important in the development of AD. Therefore, SP and NK1R antagonist or blocker agents may help to treat patients with AD. Trial registration Registration number: ChiCTR-BOC-16010279; Registration date: Dec., 28, 2016; retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in plasma of individuals with various diseases. However, the role of LRG1 in allergic airway disease has not been investigated.Objective: To explore the involvement of LRG1 in allergy and its cell origins.Methods: The expression levels of LRG1 and its receptor transforming growth factor-beta receptor II (TGFBR2) in patients with allergic rhinitis (AR) and asthma (AS) were examined by flow cytometry, and enzyme-linked immunosorbent assay (ELISA).Results: LRG1 and soluble TGFBR2 expression in plasma of patients with AR and AS were markedly lower than that of healthy control (HC) subjects. Large proportions of CD123 + HLA-DR-, CD16+, CD4+, CD8+, CD14+, and CD19+ cells expressed LRG1, although the percentages of LRG1+ cells in these cell populations were lower in AR and AS patients. Up to 89.8 and 15.5 % of dispersed mast cells expressed LRG1 and TGFBR2. Moreover, allergen extract exposure significantly reduced LRG1 and TGFBR2 expression in the plasma and leukocytes of patients with AR and AS.Conclusions: Reduced LRG1 and TGFBR2 levels in patients with allergic airway disorders are likely caused by inhibitory actions of allergens in LRG1 producing cells. Thus, LRG1 may be a key regulatory factor of allergic responses. [ABSTRACT FROM AUTHOR]