Browsing by Subject "Regulatory T cell"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Corrigendum: Regulatory T cells targeting a pathogenic MHC class II: insulin peptide epitope postpone spontaneous autoimmune diabetes
    (Frontiers Media, 2024-03-07) Obarorakpor, Nyerhovwo; Patel, Deep; Boyarov, Reni; Amarsaikhan, Nansalmaa; Cepeda, Joseph Ray; Eastes, Doreen; Robertson, Sylvia; Johnson, Travis; Yang, Kai; Tang, Qizhi; Zhang, Li; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    In the published article, there was an error in the Funding statement. Grant “JDRF 2-SRA-2018-648-S-B” grant was missing in the statement. The correct Funding statement appears below. Funding This study was supported by grants from NIH R03AI139811-01A1, DoD W81XWH2210087, JDRF 2-SRA-2018-648-S-B, and a Pilot and Feasibility Award from the CDMD NIH/NIDDK Grant Number P30 DK097512 (to LZ). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
  • Thumbnail Image
    Item
    IL-33 Mediated Th2 Effector Functions are Suppressed in Tregs by Bcl6 and Regulated by Sex
    (2024-08) Lee, Kyu Been; Dent, Alexander; Richer, Martin; Robinson, Christopher; Yang, Kai
    Allergic airway inflammation (asthma) is a prevalent and uncurable disease worldwide, affecting many individuals’ quality of life. Although asthma does not form from a singular cause, one primary mediator comes from the exposure to environmental allergens and the improper activation of the T cell subset: T helper 2 (Th2) cells. Th2 cells produce pro-inflammatory cytokines and promote the activation and recruitment of various pro-inflammatory cells into the lung, causing greater damage and inflammatory responses in the organ. Th2 cell’s activation is regulated by another T cell subset, Regulatory T (Treg) cells, by expressing anti-inflammatory cytokines and downregulating the inflammatory response. On the contrary, the release of interleukin-33 (IL-33) from damaged lung epithelial cells transitions Tregs into Th2-like Tregs (ST2+ Tregs) which release both pro-and anti-inflammatory cytokines and cannot suppress the inflammatory disease. However, transcriptional repressor protein B cell lymphoma 6 (Bcl6) provides Tregs a stable follicular phenotype and suppresses the ST2+ Treg transition. Preliminary data revealed that Bcl6 repressive function is dependent on mouse sex, in which Tregs of male mice are more resistant to the ST2+ Treg phenotype than those of female mice. However, the removal of Bcl6 also removed the sex-dependent suppression against the ST2+ Treg transition. The project therefore sought to further confirm and answer whether Bcl6 suppressed the ST2+ Treg phenotype in a sex-dependent manner, ultimately leading to a sex-biased asthma prevalence and severity. We utilized quantitative polymerase chain reaction (qPCR) and next-generation sequencing techniques to uncover which genes Bcl6 regulates, how IL-33 affects chromatin accessibility/gene expression, and what relation sex hormones have with Bcl6 in the expression of Th2 cytokines from Tregs. Currently, we have discovered that estrogen-like chemicals in common cell culturing media may be acting on the estrogen receptor of Tregs and causing differential gene expressions based on media conditions. We also determined that Bcl6 is acting independently of mouse sex to suppress Th2 genes in Tregs, contrary to preliminary findings. Overall, we have obtained insight on the role of the estrogen receptor and Bcl6’s mechanism of suppression in relation to sex.
  • Thumbnail Image
    Item
    Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes
    (Frontiers Media, 2023-08-01) Obarorakpor, Nyerhovwo; Patel, Deep; Boyarov, Reni; Amarsaikhan, Nansalmaa; Cepeda, Joseph Ray; Eastes, Doreen; Robertson, Sylvia; Johnson, Travis; Yang, Kai; Tang, Qizhi; Zhang, Li; Biostatistics and Health Data Science, School of Medicine
    Introduction: In spontaneous type 1 diabetes (T1D) non-obese diabetic (NOD) mice, the insulin B chain peptide 9-23 (B:9-23) can bind to the MHC class II molecule (IAg7) in register 3 (R3), creating a bimolecular IAg7/InsulinB:9-23 register 3 conformational epitope (InsB:R3). Previously, we showed that the InsB:R3-specific chimeric antigen receptor (CAR), constructed using an InsB:R3-monoclonal antibody, could guide CAR-expressing CD8 T cells to migrate to the islets and pancreatic lymph nodes. Regulatory T cells (Tregs) specific for an islet antigen can broadly suppress various pathogenic immune cells in the islets and effectively halt the progression of islet destruction. Therefore, we hypothesized that InsB:R3 specific Tregs would suppress autoimmune reactivity in islets and efficiently protect against T1D. Methods: To test our hypothesis, we produced InsB:R3-Tregs and tested their disease-protective effects in spontaneous T1D NOD.CD28-/- mice. Results: InsB:R3-CAR expressing Tregs secrete IL-10 dominated cytokines upon engagement with InsB:R3 antigens. A single infusion of InsB:R3 Tregs delayed the onset of T1D in 95% of treated mice, with 35% maintaining euglycemia for two healthy lifespans, readily home to the relevant target whereas control Tregs did not. Our data demonstrate that Tregs specific for MHC class II: Insulin peptide epitope (MHCII/Insulin) protect mice against T1D more efficiently than polyclonal Tregs lacking islet antigen specificity, suggesting that the MHC II/insulin-specific Treg approach is a promising immune therapy for safely preventing T1D.
  • Thumbnail Image
    Item
    Role of Orally Induced Regulatory T Cells in Immunotherapy and Tolerance
    (Elsevier, 2021) Bertolini, Thais B.; Biswas, Moanaro; Terhorst, Cox; Daniell, Henry; Herzog, Roland W.; Piñeros, Annie R.; Pediatrics, School of Medicine
    Oral antigen administration to induce regulatory T cells (Treg) takes advantage of regulatory mechanisms that the gastrointestinal tract utilizes to promote unresponsiveness against food antigens or commensal microorganisms. Recently, antigen-based oral immunotherapies (OITs) have shown efficacy as treatment for food allergy and autoimmune diseases. Similarly, OITs appear to prevent anti-drug antibody responses in replacement therapy for genetic diseases. Intestinal epithelial cells and microbiota possibly condition dendritic cells (DC) toward a tolerogenic phenotype that induces Treg via expression of several mediators, e.g. IL-10, transforming growth factor-β, retinoic acid. Several factors, such as metabolites derived from microbiota or diet, impact the stability and expansion of these induced Treg, which include, but are not limited to, FoxP3+ Treg, LAP+ Treg, and/or Tr1 cells. Here, we review various orally induced Treg, their plasticity and cooperation between the Treg subsets, as well as underlying mechanisms controlling their induction and role in oral tolerance.