Vitamin C Fosters the In Vivo Differentiation of Peripheral CD4+ Foxp3− T Cells into CD4+ Foxp3+ Regulatory T Cells but Impairs Their Ability to Prolong Skin Allograft Survival
نویسندگان
چکیده
Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs). In this study, we measured VitC transporter (SVCT2) expression in different immune cell populations, finding Tregs as one of the cell subset with the highest levels of SVCT2 expression. Unexpectedly, we found that VitC treatment reduces the ability of natural Tregs to suppress effector T cell proliferation in vitro, while having an enhancer effect on TGFβ-induced Foxp3+ Tregs. On the other hand, VitC increases iTregs generation in vitro and in vivo, however, no allograft tolerance was achieved in animals orally treated with VitC. Lastly, Tregs isolated from the draining lymph nodes of VitC-treated and transplanted mice also showed impaired suppression capacity ex vivo. Our results indicate that VitC promotes the generation and expansion of Tregs, without exhibiting CD4+ T cell-mediated allograft tolerance. These observations highlight the relevance of the nutritional status of patients when immune regulation is needed.
منابع مشابه
Induction of T Regulatory Subsets from Naïve CD4+ T Cells after Exposure to Breast Cancer Adipose Derived Stem Cells
Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast ...
متن کاملNumerical status of CD4+CD25+FoxP3+ and CD8+CD28- regulatory T cells in multiple sclerosis
Objective(s): Regulatory T cells, including CD4+CD25+Fox3+ and CD8+CD28- cells play an important role in regulating the balance between immunity and tolerance. Since multiple sclerosis is an inflammatory autoimmune disease, regulatory T cells are considered to be involved in its pathogenesis. In this study, we investigated the circulatory numbers of the two mentioned types of regulatory T cells...
متن کاملFoxP3+ Regulatory T Cells in Peripheral Blood of Patients with Epithelial Ovarian Cancer
Background: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4 +CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. Objectives: To investigate the percentage of CD4 +CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women ...
متن کاملAltered Suppressor Function of Regulatory T Cells in Type 1 Diabetes
Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in compari...
متن کاملSclareol Reduces CD4+ CD25+ FoxP3+ T-reg Cells in a Breast Cancer Model in Vivo
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects o...
متن کامل