Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis

Akiyama, Kentaro; Chen, Chider; Wang, Dandan; Xu, Xiao; Qu, Cunye; Yamaza, Takayoshi; Cai, Tao; Chen, Wanjun; Sun, Lingyun; Shi, Songtao

doi:10.1016/j.stem.2012.03.007

Cited by 626 publications

(622 citation statements)

References 34 publications

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“…Although the mechanism by which IL-17 + MSCs upregulate Th17 cells is unknown, the interplay between donor MSCs and recipient microenvironment may determine MSC-based immunomodulatory response [33,41]. Our findings imply that MSC-based immunomodulation is regulated by different subsets of MSCs, in which they may exert either immunosuppressive or immunostimulatory functions.…”

Section: Discussionmentioning

confidence: 78%

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A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

et al. 2012

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Section: Discussionmentioning

confidence: 78%

“…Previous studies indicate that MSC-based immunotherapy is a promising therapeutic approach for a variety of autoimmune diseases, including systemic sclerosis and systemic lupus erythematosus [1,6,8,33]. However, the detailed mechanism of MSC-based immune therapy is not fully elucidated [34].…”

Section: Discussionmentioning

confidence: 99%

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

et al. 2012

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“…61 Activated MSCs can modulate adaptive immune cells through contact-dependent mechanisms. These include activation of the PD-1 pathway, 62 Fas-mediated T-cell apoptosis, 63 engagement of …”

Section: Immune Modulation By Mscsmentioning

confidence: 99%

Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.

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“…Therefore, direct suppressive effects of MSCs on the immune system are short-lived, and do not explain the long-term therapeutic effects observed with MSCs in clinical and animal studies. In this context, it has been suggested that MSCs trigger a state of immune tolerance, for example, through the induction of regulatory T cells (Tregs) (6,7).…”

mentioning

confidence: 99%

Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye

Lee

Jeong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

137

109

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Intravenously administered mesenchymal stem/stromal cells (MSCs) engraft only transiently in recipients, but confer long-term therapeutic benefits in patients with immune disorders. This suggests that MSCs induce immune tolerance by long-lasting effects on the recipient immune regulatory system. Here, we demonstrate that i.v. infusion of MSCs preconditioned lung monocytes/macrophages toward an immune regulatory phenotype in a TNF-α-stimulated gene/protein (TSG)-6-dependent manner. As a result, mice were protected against subsequent immune challenge in two models of alloand autoimmune ocular inflammation: corneal allotransplantation and experimental autoimmune uveitis (EAU). The monocytes/macrophages primed by MSCs expressed high levels of MHC class II, B220, CD11b, and IL-10, and exhibited T-cell-suppressive activities independently of FoxP3 + regulatory T cells. Adoptive transfer of MSCinduced B220 + CD11b + monocytes/macrophages prevented corneal allograft rejection and EAU. Deletion of monocytes/macrophages abrogated the MSC-induced tolerance. However, MSCs with TSG-6 knockdown did not induce MHC II + B220 + CD11b + cells, and failed to attenuate EAU. Therefore, the results demonstrate a mechanism of the MSC-mediated immune modulation through induction of innate immune tolerance that involves monocytes/macrophages. corneal allotransplantation | experimental autoimmune uveitis | immune tolerance | mesenchymal stem/stromal cell | monocyte/macrophage

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Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis

Cited by 626 publications

References 34 publications

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

Stromal cells–are they really useful for GVHD?

Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye

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