Bertolini, Thais B.Biswas, MoanaroTerhorst, CoxDaniell, HenryHerzog, Roland W.Piñeros, Annie R.2023-05-172023-05-172021Bertolini TB, Biswas M, Terhorst C, Daniell H, Herzog RW, Piñeros AR. Role of orally induced regulatory T cells in immunotherapy and tolerance. Cell Immunol. 2021;359:104251. doi:10.1016/j.cellimm.2020.104251https://hdl.handle.net/1805/33042Oral 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.en-USPublisher PolicyOral toleranceOral Immunotherapy (OIT)Regulatory T cellIntestinal immune systemArticle