期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.586220
关键词
type 1 diabetes; vaccine; tolerance; microparticles; immunoregulation; autoimmunity
类别
资金
- JDRF [SRA-2016-318-S-B]
The study demonstrated that using the RA + TGF beta 1 microparticle formulation could effectively prevent hyperglycemia in non-obese diabetic mice with mid-stage active islet-selective autoimmunity. The preventive effects did not seem to be mediated by increased numbers of regulatory T-lymphocytes inside the pancreatic lymph nodes, but rather by a mild increase in the frequency of regulatory B-lymphocytes inside the mesenteric lymph nodes.
Type 1 diabetes (T1D) is a disorder of impaired glucoregulation due to lymphocyte-driven pancreatic autoimmunity. Mobilizing dendritic cells (DC) in vivo to acquire tolerogenic activity is an attractive therapeutic approach as it results in multiple and overlapping immunosuppressive mechanisms. Delivery of agents that can achieve this, in the form of micro/nanoparticles, has successfully prevented a number of autoimmune conditions in vivo. Most of these formulations, however, do not establish multiple layers of immunoregulation. all-trans retinoic acid (RA) together with transforming growth factor beta 1 (TGF beta 1), in contrast, has been shown to promote such mechanisms. When delivered in separate nanoparticle vehicles, they successfully prevent the progression of early-onset T1D autoimmunity in vivo. Herein, we show that the approach can be simplified into a single microparticle formulation of RA + TGF beta 1 with surface decoration with the T1D-relevant insulin autoantigen. We show that the onset of hyperglycemia is prevented when administered into non-obese diabetic mice that are at the mid-stage of active islet-selective autoimmunity. Unexpectedly, the preventive effects do not seem to be mediated by increased numbers of regulatory T-lymphocytes inside the pancreatic lymph nodes, at least following acute administration of microparticles. Instead, we observed a mild increase in the frequency of regulatory B-lymphocytes inside the mesenteric lymph nodes. These data suggest additional and potentially-novel mechanisms that RA and TGF beta 1 could be modulating to prevent progression of mid-stage autoimmunity to overt T1D. Our data further strengthen the rationale to develop RA+TGF beta 1-based micro/nanoparticle vaccines as possible treatments of pre-symptomatic and new-onset T1D autoimmunity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据