Mesenchymal Stem Cells Repress Th17 Molecular Program through the PD-1 Pathway

Luz‐Crawford, Patricia; Noël, Danièle; Fernández, Ximena; Khoury, Maroun; Figueroa, Fernando; Carrión, Flavio; Jørgensen, Christian; Djouad, Farida

doi:10.1371/journal.pone.0045272

Cited by 159 publications

(133 citation statements)

References 46 publications

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“…MSCs produce immunemodulatory molecules such as hepatocyte growth factor (HGF), TGF-B, and PGE2, which may enact these cellular effects [55] . MSCs have also been reported to inhibit TH17 development through various means, including inhibition with the effector molecules PGE2, a truncated peptide of C-C chemokine ligand-2 (CCL-2), IL-10, and PD-1/PD-L1 ligation [52,[60][61][62][63] . Importantly, MSCs must be pre-exposed to a combination of effector cytokines, including IFNγ and TNFα or IL-1β, in order to efficiently suppress T cell function [58] .…”

Section: Mechanisms Of Msc Suppression Of Adaptive Immune Cellsmentioning

confidence: 99%

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Glenn¹

2014

WJSC

347

290

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Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

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Section: Mechanisms Of Msc Suppression Of Adaptive Immune Cellsmentioning

confidence: 99%

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Glenn¹

2014

WJSC

347

290

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“…More than that, MSC can induce the expansion of regulatory CD4 + T cells in the periphery [25], [26] while also inhibiting Th-17 cell generation [27], [28]. Accordingly, the use of ADSC has been widespread since they can be harvested easily via liposuction and then expanded in vitro .…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

et al. 2013

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Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4+ regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4+ T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation.

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“…Nesting of MSCs in the target organ is also of importance for the immunosuppressive effects in vivo (28). In the presence of inflammatory factors, MSCs are able to migrate to injury sites and are distributed in peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with autoimmune thyroiditis

Xiuhui

Wei

et al. 2017

Experimental and Therapeutic Medicine

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The aim of the present study was to determine the repairing effects of intercellular adhesion molecule (ICAM)-1-expressing mesenchymal stem cells (MSCs) in mice with autoimmune thyroiditis. Following induction of an experimental autoimmune thyroiditis (EAT) model, mice were randomly divided into the following groups (n=10 each): i) Normal control; and experimental groups that were subject to EAT induction, including ii) EAT model; and iii) primary MSC; iv) C3H10T1/2/MSC; v) C3H10T1/2-MIGR1/MSC; and vi) C3H10T1/2-MIGR1-ICAM-1/MSC, which were all administered the relevant cells. MSCs were administered via the caudal vein. A blood sample was harvested from the angular vein of each animal 28 days post-treatment and ELISA was used to determine the serum total triiodothyronine, total thyroxine (T4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase (TPOAb), anti-thyroid microsomal (TMAb) and anti-thyroglobulin (TGAb) antibodies. Hematoxylin and eosin staining was performed to evaluate injury of the thyroid gland by determining the size of the follicle, inflammatory infiltration, colloidal substance retention and epithelial injury. Reverse transcription-quantitative polymerase chain reaction was performed to determine the mRNA expression of interleukin (IL)-4, IL-10, IL-17 and interferon (INF)-γ. Western blot analysis was performed to determine the expression of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK). To observe cellular migration in vivo, mice were divided into the following groups, (n=10 each), which were subject to EAT induction: i) CM-DiI-labeled primary MSC; ii) CM-DiI-labeled C3H10T1/2/MSC; iii) CM-DiI-labeled C3H10T1/2-MIGR1/MSC; and iv) CM-DiI-labeled C3H10T1/2-ICAM-1/MSC, which were all administered the relevant cells via the caudal vein. C3H10T1/2-ICAM-1/MSCs were able to ameliorate the expression of T4, TSH, TPOAb, TMAb and TGAb in vivo, attenuate thyroid follicle injury and decrease the splenic index in mice. They were also able to ameliorate the mRNA expression of IL-4, IL-10, IL-17 and INF-γ, and the modulation of the P38 and ERK-signaling pathways in the mouse spleen. Furthermore, ICAM-1 overexpression was able to modulate the nesting of MSCs in the thyroid gland and lung. These findings suggest that C3H10T1/2-ICAM-1/MSC may affect the differentiation, proliferation and migration of immunocytes through modulating the p38 and ERK signaling pathways, and that ICAM-1 may modulate the immunoregulatory effects of MSCs by affecting the migration of MSCs in vivo.

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Mesenchymal Stem Cells Repress Th17 Molecular Program through the PD-1 Pathway

Cited by 159 publications

References 46 publications

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with autoimmune thyroiditis

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