Role of orally induced regulatory T cells in immunotherapy and tolerance.

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-ß, 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.

Regulation of mesenchymal stem cells on CD4+LAP+Freg cells in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To investigate the immune regulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation on CD4+LAP+Treg cells in the peripheral blood of patients with systemic lupus erythematosus (SLE).Methods CD4+LAP+ Treg cells were detected in the peripheral blood from 30 SLE patients and 30 normal controls by flow cytometry.Five SLE patients received UC-MSCs transplantation,and their peripheral blood was collected before and after 24 hours of cell infusion.The percentages of CD4+ LAP+ T cells were detected by flow cytometry.Data were analyzed with t test and Spearman correlation test.Results The percentage of CD4+LAP+ Treg cells in the peripheral blood of SLE patients [(2.49 ±0.23)％]decreased remarkably compared with healthy controls [(3.35±0.19)％] (r=3.079,P＜0.01),and it was negatively correlated with serum alanine aminotransferase (ALT) [(40±44) U/L,r=-0.51,P＜0.05],AST [(35±53) U/L,r=-0.52,P＜0.05) and ALP [(64±25) U/L,r=-0.53,P＜0.01) level res-pectively.24 hours after UC-MSCs transplantation,the percentages of CD4+LAP+ Treg cells increased signif-icantly in SLE patients[(3.6±0.9)％ vs (2.1±0.6)％,r=3.508,P＜0.05].Conclusion The significantly decreased percentage of CD4+LAP+ Treg cells in patients with SLE suggests thatthey may participate in the pathogenesis of SLE.UC-MSCs transplantation can upregulate the expression of CD4+LAP+Treg cells in SLE patients,and the modulatory effects of UC-MSCs on CD4+LAP+ Treg cells may be one of the mechanisms of UC-MSCs therapy in ameliorating the disease.