Frontline Science: TLR3 activation inhibits food allergy in mice by inducing IFN-γ+ Foxp3+ regulatory T cells

Abstract

The pathologic feature of food allergy (FA) is the aberrant Th2-biased immune response in the intestine. Regulatory T cells (Tregs) play an important role in the suppression of aberrant immune response. The activities of the TLRs regulate multiple cell functions. This study aims to investigate the role of TLR3 activation in the regulation of Th2-biased immune response in the intestine by the generation of inducible Tregs (iTregs). In this study, polyinosinic polycytidylic acid (polyI:C) was used as an activator of TLR3. An FA mouse model was developed to establish the Th2-biased inflammation in the intestine. The effects of TLR3 activation on the generation of iTreg were tested in the culture and in mice. We observed that exposure to polyI:C induced IFN-+ Foxp3 + iTregs in mouse intestine and in the culture. The IFN-+ Foxp3 + iTregs showed immune suppressive functions. Exposure to polyI:C increased T-bet levels in CD4 + T cells. The T-bet formed a complex with GATA3 to dissociate Foxp3 from GATA3/Foxp3 complex in CD4 + T cells. The Foxp3 thus gained the opportunity to move to TGF-promoter to generate iTregs. Administration with polyI:C prevented the development of FA and inhibited existing FA. In conclusion, activation of TLR3 induces IFN-+ Foxp3 + Tregs, which can prevent FA development and inhibit existing FA in mice. K E Y W O R D SFood allergy, Intestine, Murine model, Regulatory T cell, TLR3

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

“…Taken together, our findings suggest that GMP protects on GI manifestations and intestinal alterations associated with FA, by shifting the immune balance towards the type 1 and regulatory profiles, and away from the type 2 response; and this effect might be mediated, at least partially, by stimulating the production of TGF-β at the intestinal level. Our results are supported by findings showing that in CD4+ T cells from FA mice GATA3 forms a complex with Foxp30 that prevents Foxp3 movement to TGF-β promoter locus [ 103 ]. When T-bet expression is increased, it binds GATA3 and dissociates Foxp3, which has the opportunity to move to TGF-β promoter.…”

The alleviated symptoms in ovalbumin‐allergic mice treated with selenium‐enriched tea polysaccharide by modulation of intestinal flora and gut metabolites

“…As a typical cytokine secreted by Th2 cells, IL-4 stimulates B lymphocytes differentiation and IgE production, thereby inducing mast cell degranulation and aggravating allergic reactions (Anna et al, 2023). As cytokine secreted by Th1 cells, IFN-γ can reduce the inflammatory response caused by FA, and its increase will inhibit the secretion of Th2 cytokines (Hong et al, 2019). In the present study, ies, Lachnospiraceae_NK4A136_group is a potential probiotic involved in the Hsp70-NF-κB signaling to ameliorate colonic damage and inflammation caused by FA (Liu et al, 2023).…”

“…As a typical cytokine secreted by Th2 cells, IL‐4 stimulates B lymphocytes differentiation and IgE production, thereby inducing mast cell degranulation and aggravating allergic reactions (Anna et al., 2023). As cytokine secreted by Th1 cells, IFN‐γ can reduce the inflammatory response caused by FA, and its increase will inhibit the secretion of Th2 cytokines (Hong et al., 2019). In the present study, it was found that the serum levels of Th1 type cytokine IFN‐γ were increased, whereas the Th2 type cytokine IL4 was decreased after the intervention of Se‐TPS.…”

Specific antigen‐guiding exosomes inhibit food allergies by inducing regulatory T cells

“…24 Treg generation has been employed in the studies of FA treatment. 24,25 In addition, generating Tregs is one of the major goals in Ag-specific immunotherapy. 26 The present study added IL-2 into the mExosomes.…”