Chimeric specific antigen epitope‐carrying dendritic cells induce interleukin‐17(+) regulatory T cells to suppress food allergy

Abstract

Food allergies (FAs) affect about 2%-8% of the world's population. FA clinical symptoms vary from slight abdominal discomfort to life-threatening anaphylactic shock. 1 The basic FA pathological changes are Th2 polarization-related inflammation, including the over production of antigen (Ag)-specific IgE, Th2 cytokines (eg interleukin [IL]-4, IL-5 and IL-13), profound infiltration of eosinophils and mast cells in tissues. 2 Th2 cytokines, especially IL-4, induce plasma cells to produce IgE. IgE binds to the high-affinity IgE receptors on the surface Abstract Background: The on-purpose-modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases. Objective: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP-DCs) to induce interleukin (IL)-17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model. Methods: In this study, we constructed CAP-DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti-DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA-FA model was developed to test the effects of CAP-DCs on suppressing the allergic response in the intestine. Results: The CAP-DCs are characterized as that a complex of scFv-IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL-6, IL-23, transforming growth factor (TGF)-β and CCR9. After being passively transferred with CAP-DCs or injection of scFv-IC, Ag-specific IL-17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag-specific Th2 response. FA mice were adoptively transferred with the CAP-DCs or scFv-IC injection, which resulted in a significant decrease in the number of Ag-specific Th2 cells and suppression of FA response in an Ag-specific manner. Conclusions and Clinical Relevance: CAP-DCs can ameliorate FA response by inducing Ag-specific IL-17+ Foxp3+ iTregs and suppressing Ag-specific Th2 response. To generate CAP-DCs has the translational potential in the treatment of FA. K E Y W O R D S dendritic cell, epitope, food allergy, immune regulation, immunotherapy

Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL‑17 via the Bax/Bcl‑2 signaling pathway

“…However, Iida et al (33) revealed that the survival time of patients with high IL-17 mRNA expression levels was significantly longer compared with those with low IL-17 mRNA expression levels by detecting the IL-17 mRNA expression levels in the peritoneal lavage of patients with gast fric carcinoma following surgery. Previous studies have also demonstrated that tumor growth and distant metastasis in IL-17 deficient mice were significantly increased compared with those in the control group, suggesting that IL-17 could enhance the antitumor immunity of local T cells in tumors (34,35). The present study investigated the effects of IL-17 in gastric carcinoma.…”

Developments in the field of allergy in 2020 through the eyes of Clinical and Experimental Allergy

“…This coincided with a number of studies evaluating the burden of peanut allergy and calling for improved protection for people with food allergy 69‐71 . Investigation of component IgE as a marker for ingestion, an immunological target and a discriminator with added diagnostic value also continues to be a busy area of science 72‐79 . Characteristics of infant food anaphylaxis were defined in one of the most extensive published series—hives, hypotonia and hypotension were common features in a French series with 61 infant cases, compared with 386 cases in preschool children 80 .…”

Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms

“…[21][22][23] Xu and colleagues constructed a fusion protein consisting of an epitope of the ovalbumin (OVA) molecule and a segment of the anti-DEC205 antibody, scFv. 24 The fusion protein termed chimeric Ag peptide (CAP), specifically, binds DEC205 and present on the surface of DCs. The authors show that exposure of bone marrow-derived DCs to scFv-IC fusion protein led to DC uptake of scFv-IC and also surface expression.…”

“…DEC‐205 (CD205) is a 205 kDa endocytotic receptor predominantly expressed by DCs and thymic epithelial cells and is thought to act as a cell surface receptor for CpG oligonucleotides and promote DC immunoregulatory activity 21‐23 . Xu and colleagues constructed a fusion protein consisting of an epitope of the ovalbumin (OVA) molecule and a segment of the anti‐DEC205 antibody, scFv 24 . The fusion protein termed chimeric Ag peptide (CAP), specifically, binds DEC205 and present on the surface of DCs.…”