Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy

Abstract

Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.

A Novel Framework to Predict Breast Cancer Prognosis Using Immune-Associated LncRNAs

“…Wang et al (2019) reported that TReg cells play a major role in the development of immunosuppressive tumor microenvironment mainly through cytokine signal transductions-a key determinant of immunosuppressive potential and unfavorable clinical outcomes. Inconsistent with these findings, we found that BC patients with a high TReg level had a better prognosis than those with a low TReg level (Takasato et al, 2020). The origin of tumor-infiltrating TReg cells and their association with circulating TReg cells are rarely reported, which will be explained in the follow-up study in our following publications.…”

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

“…There is growing evidence that MCs play an important role in inhibiting allergic reactions and inflammation. It has been found that oral immunotherapy (OIT)-induced desensitized MCs have a robust regulatory function and can cooperate with Tregs to form a regulatory network, which helps control food allergy [ 8 ]. It has been reported that the anti-allergic part of MCs is mainly realized through the production of regulatory cytokines, such as IL-2 and IL-10 [ 8 ].…”

“…It has been found that oral immunotherapy (OIT)-induced desensitized MCs have a robust regulatory function and can cooperate with Tregs to form a regulatory network, which helps control food allergy [ 8 ]. It has been reported that the anti-allergic part of MCs is mainly realized through the production of regulatory cytokines, such as IL-2 and IL-10 [ 8 ]. Several studies have found that the inhibition of the immune responses in the skin, intestines and bladder by MCs depends on IL-10 [ 22 ].…”

“…Thymic-derived Tregs are a type of suppressive T cell, which accounts for 5–10% of circulating CD4 + T cells [ 129 ]. Studies have shown that Tregs can reduce the production of allergen-specific IgE and pathogenic Th2 and inhibit the degranulation of MCs and basophils, which push forward an immense influence on the control of allergic symptoms [ 8 , 130 ]. Tregs impairment is related to a loss of tolerance, autoimmunity and allergy [ 130 ].…”

“…MCs appear to play an immunomodulatory role in allergic, acute, and chronic inflammation (e.g., fibrosis [ 6 , 7 ]). There is growing evidence that MCs play an enormous role in allergic responses, inflammatory responses, and wound healing [ 6 , 8 , 9 ]. In view of the high heterogeneity and plasticity of MCs, MCs-mediated immune diseases are very complex, so many diseases have not yet been properly treated (e.g., food allergy [ 10 , 11 ]).…”