期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 94, 期 8, 页码 747-762出版社
WILEY
DOI: 10.1038/icb.2016.34
关键词
-
资金
- Marie Curie Intra European Fellowship within the 7th European Community Framework Programme
- Dr Ake Olsson Foundation
- KI research foundations
- Vetenskapsradet Medicine and Health [2011-3264]
- Torsten Soderberg Foundation
- FP7 STATegra
- AFA Insurance
- Stockholm County Council
- Leonardo da Vinci Program (EU LLP)
- Swedish Medical Research Council
- BarnCancerFonden
- AlzheimerFonden
- CancerFonden
- Karolinska Institutet
- Swedish Research Council Medicine [521-2012-2770]
- Swedish Cancer Foundation
- Cancer Research Foundations of Radiumhemmet
- Cancer and Allergy Foundation
- Swedish Heart-Lung Foundation
- Karolinska Institute
While pro-inflammatory immune responses are a requirement to combat microbes, uncontrolled self-directed inflammatory immune responses are the hallmark of autoimmune diseases. Restoration of immunological tolerance involves both suppression of ongoing tissue-destructive immune responses and re-education of the host immune system. Both functionally immunosuppressive macrophages (M2) and regulatory T cells (Tregs) are implicated in these processes. Their mutual interaction is synergistic in this context and adoptive transfer of each cell type has been functioning as immunotherapy in experimental models, being particularly effective when using M2 macrophages generated with an optimized interleukin-4 (IL-4)/interleukin-10 (IL-10)/transforming growth factor-beta (TGF-beta) combination. As a prerequisite for eventual translation of M2 therapy into clinical settings we herein studied the induction, stability and mechanism of generation of human induced Tregs (iTregs) by M2 macrophages generated with IL-4/IL-10/TGF-beta. The supernatants of monocyte-derived human M2 macrophages robustly induced FOXP3 and other Treg signature molecules such as CTLA-4 and IKZF4 in human naive CD4 T cells. M2-induced iTregs displayed enhanced FOXP3 stability and low expression of pro-inflammatory cytokines interferon-gamma and IL-17, as well as functional immunosuppressive activity compared with control T cells. The FOXP3-inducing activity was dependent on TGF-beta, which was both expressed and captured with re-release by M2 macrophages into the soluble supernatant fraction, in which the TGF-beta was not confined to extracellular vesicles such as exosomes. We propose that adoptive transfer of human M2 macrophages may be exploited in the future to induce Tregs in situ by delivering TGF-beta, which could be developed as a therapeutic strategy to target autoimmune and other inflammatory diseases.
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