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Updated: Apr 28, 2026
In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis
Shipeng Dang1, Huanbai Xu2, Congfeng Xu1
1Key Laboratory of Stem Cell Biology; Institute of Health Sciences; Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine (SJTUSM); and Shanghai Institute of Immunology; Institutes of Medical Sciences; SJTUSM; Shanghai, China.
Abstract:
Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4(+) T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy.
Insights
Inhibiting autophagy in mesenchymal stem cells (MSCs) enhances their ability to treat multiple sclerosis models. This approach boosts MSC immunosuppressive function by increasing reactive oxygen species and MAPK activation, improving T cell suppression.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cell (MSC) therapy shows promise for inflammatory diseases like multiple sclerosis.
- The behavior and function of MSCs within the inflammatory environment of multiple sclerosis are not fully understood.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying multiple sclerosis.
Purpose of the Study:
- To investigate the role of autophagy in MSCs during EAE treatment.
- To determine how inflammatory cytokines influence autophagy in MSCs.
- To explore the potential of modulating autophagy to enhance MSC therapeutic efficacy.
Main Methods:
- Induction of autophagy in MSCs using inflammatory cytokines (interferon gamma, tumor necrosis factor).
- Inhibition of autophagy via BECN1 knockdown and pharmacological agents.
- Assessment of MSC therapeutic effects on EAE, including CD4(+) T cell suppression.
- Analysis of reactive oxygen species generation, MAPK activation, and prostaglandin E2 expression.
Main Results:
- Autophagy is induced in MSCs within the inflammatory milieu of EAE.
- Inhibition of autophagy significantly improved MSC therapeutic effects in EAE by enhancing CD4(+) T cell suppression.
- Autophagy inhibition led to increased reactive oxygen species and MAPK activation in MSCs.
- This pathway was crucial for PTGS2 and prostaglandin E2 expression, mediating immunoregulatory function.
Conclusions:
- Inflammatory microenvironment-induced autophagy impairs the immunosuppressive function of MSCs.
- Modulating autophagy in MSCs presents a novel strategy to enhance their efficacy in immunotherapy for multiple sclerosis.
- Targeting autophagy could optimize MSC-based treatments for inflammatory and autoimmune disorders.
Related Concept Videos
01:19Mesenchymal Stem Cells
01:27Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...