Myeloid‐Derived Suppressor Cells Limit the Inflammation by Promoting T Lymphocyte Apoptosis in the Spinal Cord of a Murine Model of Multiple Sclerosis

Moliné-Velázquez, Verónica; Cuervo, Henar; Sol, Virginia Vila-del; Ortega, María Cristina; Clemente, Diego; Castro, Fernando de

doi:10.1111/j.1750-3639.2011.00495.x

Cited by 110 publications

(117 citation statements)

References 55 publications

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“…the 'traditional' animal model of MS) resulted in tolerance to myelin antigens in the periphery and thus protection from EAE. Additionally, evidence of immunosuppression by myeloid-derived suppressor cells, including monocytes and granulocytes, may be via the urea cycle enzyme arginase-I [37][38][39]; here, we identify a significant increase in the abundance of arginase-I in the spleens of cuprizone-treated mice. Myeloid-derived suppressor cells expressing increased levels of arginase-I may thus potentially contribute to the apparent lack of T cell involvement in the cuprizone model.…”

Section: Discussionmentioning

confidence: 52%

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

et al. 2015

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An initial proteomic analysis of the cuprizone mouse model to characterise the breadth of toxicity by assessing cortex, skeletal muscle, spleen and peripheral blood mononuclear cells. Cuprizone treated vs. control mice for an initial characterisation. Select tissues from each group were pooled, analysed in triplicate using two-dimensional gel electrophoresis (2DE) and deep imaging and altered protein species identified using liquid chromatography tandem mass spectrometry (LC/MS/MS). Forty-three proteins were found to be uniquely detectable or undetectable in the cuprizone treatment group across the tissues analysed. Protein species identified in the cortex may potentially be linked to axonal damage in this model, and those in the spleen and peripheral blood mononuclear cells to the minimal peripheral immune cell infiltration into the central nervous system during cuprizone mediated demyelination. Primary oligodendrocytosis has been observed in type III lesions in multiple sclerosis. However, the underlying mechanisms are poorly understood. Cuprizone treatment results in oligodendrocyte apoptosis and secondary demyelination. This initial analysis identified proteins likely related to axonal damage; these may link primary oligodendrocytosis and secondary axonal damage. Furthermore, this appears to be the first study of the cuprizone model to also identify alterations in the proteomes of skeletal muscle, spleen and peripheral blood mononuclear cells. Notably, protein disulphide isomerase was not detected in the cuprizone cohort; its absence has been linked to reduced major histocompatibility class I assembly and reduced antigen presentation. Overall, the results suggest that, like experimental autoimmune encephalomyelitis, results from the standard cuprizone model should be carefully considered relative to clinical multiple sclerosis.

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Section: Discussionmentioning

confidence: 52%

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

et al. 2015

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“…The MDSCs consist of a heterogeneous cell population in the blood and spleen of naive mice (17). These MDSCs can suppress anti-CD3/28-induced T cell proliferation, downregulate CD3ε-chain expression (18), inhibit CD8 T cell cytotoxicity (19), induce T cell apoptosis (20), and reduce the cytotoxicity of NK cells and activation of NKT cells (21). Such suppressive activities are mediated by L-arginine metabolic pathways (22), (23).…”

mentioning

confidence: 99%

α-Galactosylceramide but Not Phenyl-Glycolipids Induced NKT Cell Anergy and IL-33–Mediated Myeloid-Derived Suppressor Cell Accumulation via Upregulation of egr2/3

Huang

Tsai

Chang

et al. 2014

The Journal of Immunology

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Strategies for cancer immunotherapy include activating immune system for therapeutic benefit or blockade of immune checkpoints. To harness innate immunity to fight cancer, a-galactosylceramide (a-GalCer) has been used to activate NKT cells. Unfortunately, administration of a-GalCer causes long-term NKT cell anergy, but the molecular mechanism is unclear. In this study, we showed that a-GalCer-triggered egr2/3, which induced programmed death 1 and cbl-b in NKT cells, leading to NKT cell anergy. We also uncovered the induction of the immunosuppressive myeloid-derived suppressor cells (MDSCs) in the spleen by a-GalCer that might attenuate its antitumor efficacy. The accumulation of MDSC was accompanied by 20-fold rise in their arg-1 mRNAs and enhanced expression of programmed death 1/programmed death ligand 1. Furthermore, a-GalCer-induced egr-2/3 in hepatic NKT cells upregulated their TRAIL in addition to Fas ligand (FasL) and induced alarm signaling molecule IL-33 in Kupffer cells, presumably because of liver damage triggered by TRAIL/FasL. We further demonstrated that IL-33-stimulated macrophages produce G-CSF, which in turn, boosted MDSCs. Thus, a-GalCer-induced FasL/TRAIL and IL-33 provided a novel mechanism underlying a-GalCer-induced hepatotoxicity and MDSC accumulation. In contrast, analogs of a-GalCer containing phenyl group in the lipid tail could neither induce NKT anergy nor enhance MDSCs accumulation. Furthermore, tumor-infiltrating MDSCs in mice injected repeatedly with a-GalCer were 2-fold higher than those treated with phenyl-glycolipids. These results not only revealed the induction of MDSC via IL-33 as a new mechanism for a-GalCer-elicited immunosuppression but also provided one of the mechanisms underlying the superior antitumor potency of phenyl-glycolipids. Our findings have important implications for the development of NKT-stimulatory glycolipids as vaccine adjuvants and anticancer therapeutics.

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“…Studies using the multiple sclerosis mouse model, EAE, revealed that MDSCs were present in the demyelinated areas of the spinal cord tissue of mice (56). This EAE model demonstrated that MDSC accumulation in the spleen correlated with disease progression (56).…”

Section: Mdscs and Experimental Autoimmune Myocarditis (Eam)mentioning

confidence: 91%

“…This EAE model demonstrated that MDSC accumulation in the spleen correlated with disease progression (56). They identified that the CD11b + monocytes are critical for an IFN-γ-dependent negative feedback loop that suppresses autoreactive CD4 + T cells and abrogates autoimmune myocarditis (51).…”

Section: Mdscs and Experimental Autoimmune Myocarditis (Eam)mentioning

confidence: 99%

Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders

Barnie

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Myeloid-derived suppressor cells (MDSCs) were originally described as a heterogeneous population of immature cells derived from myeloid progenitors with immune-suppressive functions in tumor-bearing hosts. In recent years, increasing number of studies have described various populations of myeloid cells with MDSC-like properties in murine models of cancer and autoimmune diseases. These studies have observed that the populations of MDSCs are increased during inflammation and autoimmune conditions. In addition, MDSCs can effectively suppress T cell responses and modulate the activity of natural killer cells and other myeloid cells. MDSCs have also been implicated in the induction of regulatory T cell production. Furthermore, these cells have the potential to suppress the autoimmune response, thereby limiting tissue injury. Myeloid regulatory cells (Mregs) are recently attracting increasing attention, since they function in proinflammatory and immune suppression in autoimmune diseases, as well as in various types of cancer. Currently, research focus is directed from MDSCs to Mregs in cancer and autoimmune diseases. The present study reviewed the suppressive roles of MDSCs in various autoimmune murine models, the immune modulation of MDSCs to T helper 17 lymphocytes, as well as the proinflammatory and immunosuppressive roles of Mregs in various types of cancer and autoimmune diseases.

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Myeloid‐Derived Suppressor Cells Limit the Inflammation by Promoting T Lymphocyte Apoptosis in the Spinal Cord of a Murine Model of Multiple Sclerosis

Cited by 110 publications

References 55 publications

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis

α-Galactosylceramide but Not Phenyl-Glycolipids Induced NKT Cell Anergy and IL-33–Mediated Myeloid-Derived Suppressor Cell Accumulation via Upregulation of egr2/3

Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders

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