Sirolimus enhances the effect of apoptotic cell infusion on hematopoietic engraftment and tolerance induction

Bonnefoy, Francis; Masson, Emeline; Perruche, Sylvain; Marandin, Aliette; Borg, Christophe; Radlovic, Amandine; Shipman, Benjamin; Tiberghien, Pierre; Saas, Philippe; Kleinclauss, F.

doi:10.1038/sj.leu.2405061

Cited by 18 publications

(30 citation statements)

References 12 publications

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“…In these two settings, Treg commitment by PDCs was profoundly inhibited (Fig. 5D) + T cells at day 8 after infusion in the spleen (7,29). This increase was inhibited by macrophage depletion (7).…”

Section: Apoptotic Cells Create An Environment Favoring Treg Inductiomentioning

confidence: 92%

Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Bonnefoy

Perruche

Couturier

et al. 2011

The Journal of Immunology

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Several APCs participate in apoptotic cell-induced immune modulation. Whether plasmacytoid dendritic cells (PDCs) are involved in this process has not yet been characterized. Using a mouse model of allogeneic bone marrow engraftment, we demonstrated that donor bone marrow PDCs are required for both donor apoptotic cell-induced engraftment and regulatory T cell (Treg) increase. We confirmed in naive mice receiving i.v. syngeneic apoptotic cell infusion that PDCs from the spleen induce ex vivo Treg commitment. We showed that PDCs did not interact directly with apoptotic cells. In contrast, in vivo macrophage depletion experiments using clodronate-loaded liposome infusion and coculture experiments with supernatant from macrophages incubated with apoptotic cells showed that PDCs required macrophage-derived soluble factors—including TGF-β—to exert their immunomodulatory functions. Overall, PDCs may be considered as the major APC involved in Treg stimulation/generation in the setting of an immunosuppressive environment obtained by apoptotic cell infusion. These findings show that like other APCs, PDC functions are influenced, at least indirectly, by exposure to blood-borne apoptotic cells. This might correspond with an additional mechanism preventing unwanted immune responses against self-antigens clustered at the cell surface of apoptotic cells occurring during normal cell turnover.

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Section: Apoptotic Cells Create An Environment Favoring Treg Inductiomentioning

confidence: 92%

Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Bonnefoy

Perruche

Couturier

et al. 2011

The Journal of Immunology

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“…The injection of apoptotic splenocytes has been shown to attenuate acute cardiac allograft rejection in rats [77] and mice [91] and ameliorate chronic allograft vasculopathy in mice [80]. In addition, gamma-irradiated splenocytes promote allogeneic bone marrow engraftment [83,84,92]. The infusion of apoptotic leukocytes 7 days before the administration of allogeneic pancreatic islets has been shown to improve transplant survival through the modulation of regulatory T-cells [81].…”

Section: Pre-clinical Application Of Nucleated Apoptotic Cellsmentioning

confidence: 99%

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

Beer¹,

Mildner²,

Gyöngyösi³

et al. 2018

Cell Engineering and Regeneration

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stroke, and wound healing. In this review we describe the benefits of choosing PBMCs instead of stem cells in regenerative medicine and characterize the factors released from apoptotic PBMCs. We also discuss pre-clinical studies with apoptotic cell-based therapies and regulatory issues that have to be considered when conducting clinical trials using cell secretome-based products. This should allow the reader to envision PBMC secretome-based therapies as alternatives to all other forms of cell-based therapies.

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“…Most of the studies report the prevention of the disease, which means that apoptotic cells were infused during the triggering stage of the disease (i.e., at immunization with autoantigens or at the time of transplantation) or before the disease occurred. This is true for Type 1 diabetes in nonobese diabetic mice [47], experimental autoimmune encephalomyelitis [12,62,106], arthritis [36,107,108], fulminant hepatitis [109], contact hypersensitivity [110][111][112], acute and chronic graft rejection [86,[113][114][115], hematopoietic cell engraftment [2,14,85,116,117], acute GvHD disease [14] and reduction of infarction size after acute myocardial infarction [118,119]. Thus, it is difficult to transpose this in the clinical setting where, in general, the disease is already present when a therapeutic solution has to be found.…”

Section: Preclinical Data Using Early Apoptotic Cell Infusion In Expementioning

confidence: 99%

“…The infused apoptotic cell number and the schedule of infusion are relatively homogeneous among the different studies: 5 × 10 5 -10 7 in mice [2,12,14,36,48,63,85,86,92,106,107,[109][110][111][112][113][114][115][116][117]121,122], or 8 × 10 6 -10 8 in rats [108,118,119]. In general, only one infusion was performed (18 out of 21).…”

Section: Hematopoietic Engraftmentmentioning

confidence: 99%

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

2013

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Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

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Sirolimus enhances the effect of apoptotic cell infusion on hematopoietic engraftment and tolerance induction

Cited by 18 publications

References 12 publications

Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

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