期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 13, 期 584, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaw9668
关键词
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资金
- National Key Research and Development Program of China [2016YFC1101400]
- National Natural Science Foundation of China [81601606, 31800817, 31670995]
- Young Elite Scientist Sponsorship Program by CAST [2017QNRC001]
- Fundamental Research Funds for the Central Universities, open fund of the State Key Laboratory of Military Stomatology [2017KA02]
- Knowledge Innovation Program of Shenzhen [JCYJ20170816100941258]
- Intramural Research Program of NIH, NIDCR
- ARC Centre of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- ARC Laureate Fellowship program [FL150100060]
A novel therapeutic approach utilizing immune-homeostatic microparticles (IHMs) was developed to induce apoptosis in activated T cells, reestablish regulatory T cells, and treat multiple mouse models of autoimmunity. This strategy shows promise for efficiently treating autoimmune diseases by promoting immune tolerance.
The therapeutic goal for autoimmune diseases is disease antigen-specific immune tolerance without nonspecific immune suppression. However, it is a challenge to induce antigen-specific immune tolerance in a dysregulated immune system. In this study, we developed immune-homeostatic microparticles (IHMs) that treat multiple mouse models of autoimmunity via induction of apoptosis in activated T cells and reestablishment of regulatory T cells. Specifically, in an experimental model of colitis, IHMs rapidly released monocyte chemotactic protein-1 after intravenous administration, which recruited activated T cells and then induced their apoptosis by conjugated Fas ligand on the IHM surface. This triggered professional macrophages to ingest apoptotic T cells and produce high quantities of transforming growth factor-beta, which drove regulatory T cell differentiation. Furthermore, the modular design of IHMs allowed IHMs to be engineered with the autoantigen peptides that can reduce disease in an experimental autoimmune encephalomyelitis mouse model and a nonobese diabetic mouse model. This was accomplished by sustained release of the autoantigens after induction of T cell apoptosis and transforming growth factor-beta production by macrophages, which promoted to establish an immune tolerant environment. Thus, IHMs may be an efficient therapeutic strategy for autoimmune diseases through induction of apoptosis and reestablishment of tolerant immune responses.
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