Sca-1+Lin−CD117− Mesenchymal Stem/Stromal Cells Induce the Generation of Novel IRF8-Controlled Regulatory Dendritic Cells through Notch–RBP-J Signaling

Liu, Xingxia; Ren, Shaoda; Ge, Chaozhuo; Chen, Kai; Zenke, Martin; Keating, Armand; Zhao, Robert Chunhua

doi:10.4049/jimmunol.1402641

Cited by 24 publications

(14 citation statements)

References 59 publications

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“…Our previous study showed that co-culture with MSCs could decrease the differentiation of cDC from human CD34+ cells, while increasing the differentiation of pDC through PGE2 [22]. Furthermore, the induction of IL-10-dependent regulatory dendritic cells and IRF8-controlled regulatory dendritic cells from HSC were also reported in rats [23,24]. MSCs could also induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population [25].…”

Section: Discussionmentioning

confidence: 96%

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

Leng¹,

Zhu²,

Hou³

et al. 2020

Aging and disease

1,040

1,554

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A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in 217 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokinesecreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b mid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2and TMPRSS2which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

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Section: Discussionmentioning

confidence: 96%

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

Leng¹,

Zhu²,

Hou³

et al. 2020

Aging and disease

1,040

1,554

View full text Add to dashboard Cite

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“…The ability of DCs to migrate out of the tumor and into the draining lymph nodes is also impaired in tumor microenvironment. Recently, regulatory DC subsets, which are involved in the induction of tolerance or downregulation of immune responses, have been considered as another potential mechanism for tumor immune escape.…”

Section: Discussionmentioning

confidence: 99%

β‐glucan restores tumor‐educated dendritic cell maturation to enhance antitumor immune responses

Ning

Zhang

et al. 2016

Intl Journal of Cancer

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Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of b-glucan on TEDCs and found that b-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with b-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that b-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for b-glucan in immunotherapy and suggesting its potential clinical benefit. b-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses.

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“…Recent evidence has suggested that adipose-derived MSCs may also have a more potent immunosuppressive effect in vitro than their bone marrow-derived counterparts IDO, PGE2, M-CSF, IL-6, IL-10, and TGF-b. IDO suppresses T and natural killer (NK) cells; PGE2 suppresses B cells and inhibits their differentiation into antibody-producing plasma cells [161], as well as prevent DC maturation in conjunction with M-CSF, IL-6, IL-10, and TGF-b [156,159,[162][163][164][165].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Exploring cell-based tolerance strategies for hand and face transplantation

Fryer

Grahammer

Khalifian

et al. 2015

Expert Review of Clinical Immunology

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Broader clinical application of reconstructive hand and face transplantation is hindered by the need for lifelong immunosuppression for allograft maintenance. In this review, we summarize various cell-based approaches to tolerance induction currently under investigation in both clinical and pre-clinical models to alleviate the need for chronic immunosuppression. These include strategies to induce mixed hematopoietic chimerism, therapy with T and B regulatory cells, regulatory macrophages, tolerogenic dendritic cells, and mesenchymal stem cells. The vascularized, intragraft bone components inherent to reconstructive transplants serve as a continuous source of donor-derived hematopoietic cells, and make hand and face transplants uniquely well suited for cell-based approaches to tolerance that may ultimately tilt the risk-benefit balance for these life-changing, but not life-saving, procedures.

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Sca-1+Lin−CD117− Mesenchymal Stem/Stromal Cells Induce the Generation of Novel IRF8-Controlled Regulatory Dendritic Cells through Notch–RBP-J Signaling

Cited by 24 publications

References 59 publications

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

β‐glucan restores tumor‐educated dendritic cell maturation to enhance antitumor immune responses

Exploring cell-based tolerance strategies for hand and face transplantation

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