Crucial Role of Granulocytic Myeloid-Derived Suppressor Cells in the Regulation of Central Nervous System Autoimmune Disease

Ιωάννου, Μαριάννα; Alissafi, Themis; Lazaridis, Iakovos; Deraos, George; Matsoukas, John; Gravanis, Achille; Mastorodemos, Vasileios; Plaitakis, Andreas; Sharpe, Arlene H.; Boumpas, Dimitrios T.; Verginis, Panayotis

doi:10.4049/jimmunol.1101816

Cited by 205 publications

(236 citation statements)

References 67 publications

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“…An analysis of MDSCs subsets in the liver and spleen revealed that the number of G-MDSCs was higher in infected BALB/c with respect to B6 mice, suggesting a protective role for G-MDSCs in the resolution of inflammation. In agreement with this concept, an increased accumulation of G-MDSCs has been correlated with reduced tissue injury in various experimental models of inflammation [30][31][32]. In cancer, the frequency of each MDSCs subset appears to be influenced by the type of tumor [2].…”

Section: Discussionsupporting

confidence: 56%

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

et al. 2013

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Myeloid-derived suppressor cells (MDSCs Keywords: Inflammation r MDSCs r Nitric oxide r ROS r Trypanosoma cruziAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMyeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population consisting of immature macrophages, granulocytes, and dendritic cells as well as myeloid progenitor cells. They are considered to be one of the major components of the immune suppressive network responsible for suppressing T-cell responses in pathological conditions [1,2] as well as in the regulation of the immune response in healthy individuals [3]. These Correspondence: Dr. Susana Gea e-mail: sgea@fcq.unc.edu.ar myeloid cells are commonly identified in mice by the co-expression of the surface markers CD11b and Gr1 (Ly6G/Ly6C) and have been divided into two subsets: granulocytic (G) MDSCs with a CD11b + LY6G + LY6C low phenotype and monocytic (M) MDSCs with CD11b + LY6G − LY6C high phenotype [3,4]. Despite their morphological similarities, G-MDSCs and neutrophils are functionally and phenotypically different. G-MDSCs, but not neutrophils, are immunosuppressive and express higher levels of arginase-1 and myeloperoxidase than neutrophils, and also have increased production of reactive oxygen species (ROS) [5,6]. Although * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2014. 44: 184-194 Immunomodulation 185 M-MDSCs and inflammatory monocytes share the same phenotype and morphology, these cells are functionally distinct since M-MDSCs are highly immunosuppressive and they express high levels of both iNOS and arginase-1. Furthermore, although iNOS expression is a hallmark of a tumoricidal/microbicidal phenotype in M1 macrophages, iNOS promotes suppressive activities in M-MDSCs. This shift in iNOS activity most likely reflects the crosstalk of iNOS with other enzymes such as NADPH oxidase to promote the production of peroxynitrites, which inhibits the proliferation and effector function of T cells [2]. MDSCs use several mechanisms in addition to the production of ROS and NO, such as triggering apoptosis of activated T cells by depleting of L-arginine, via arginase [7][8][9][10]. There is also evidence that MDSCs may suppress immune activation by inducing T regulatory cell expansion [11]. Other suppressive mechanisms that have recently been proposed include the production of TGF-β [12,13], depletion of cysteine [8], induction of COX2 and prostaglandin E2 [1,[14][15][16].Trypanosoma cruzi an obligate intracellular protozoan, is the causative agent of Chagas disease. This disease affects about 20 million people in Latin America, with 120 million persons at risk. In the past decades, mainly as a result of increased migrations, the diagnosed cases have also increased in nonendemic countries such as Canada, United States of America, and Europe. This has led to an increased risk of transmission of the infection, mainly through blood transfusion and organ transplantation [17]. Pa...

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Section: Discussionsupporting

confidence: 56%

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

et al. 2013

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“…In mice, MDSCs are characterized by the coexpression of the myeloid-cell lineage differentiation Ag Gr-1 and CD11b, and can be further divided based on their morphology as monocytic or granulocytic MDSCs (26). Recently, we demonstrated a potent role of granulocytic MDSCs in suppressing autoimmune brain inflammation in mice and T cell responses in patients with multiple sclerosis in vitro (27). Specifically, MDSCs were significantly accumulated in the peripheral lymphoid compartments of mice with EAE, and they suppressed autoimmune responses in a PD-L1-dependent manner.…”

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confidence: 99%

In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

Ιωάννου

Alissafi

Boon

et al. 2013

The Journal of Immunology

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Autoimmunity ensues upon breakdown of tolerance mechanism and priming of self-reactive T cells. Plasmacytoid dendritic cells (pDCs) constitute a unique cell subset that participates in the activation of autoreactive T cells but also has been shown to be critically involved in the induction of self-tolerance. However, their functional importance during the priming phase of an organ-specific autoimmune response remains unclear. In this study, we demonstrate that absence of pDCs during myelin antigenic challenge resulted in amelioration of experimental autoimmune encephalomyelitis and reduced disease severity. This was accompanied by significantly decreased frequency of myelin-specific T cells in the draining lymph nodes and inhibition of Th1 and Th17 immune responses. Unexpectedly, in vivo ablation of pDCs increased myelopoiesis in the bone marrow and specifically induced the generation of CD11bhiGr1+ myeloid-derived suppressor cells (MDSCs). Furthermore, we demonstrate that pDC depletion enhanced the mobilization of MDSCs in the spleen, and that sorted MDSCs could potently suppress CD4+ T cell responses in vitro. Importantly, pDC-depleted mice showed increased levels of MCP-1 in the draining lymph nodes, and in vivo administration of MCP-1 increased the frequency and absolute numbers of MDSCs in the periphery of treated mice. Together, our results reveal that absence of pDCs during the priming of an autoimmune response leads to increased mobilization of MDSCs in the periphery in an MCP-1–dependent manner and subsequent amelioration of autoimmunity.

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“…Stimulated T cells (anti-CD3/CD28) from PBMCs showed lower proliferative capability in the presence of autologous RASF than in its absence, suggesting that MDSCs present in RASF may be essential to negatively regulate local T cell expansion and inflammation/autoimmunity even though these cells may contribute to collateral damage to joint tissues. Iannou et al (2012) evaluated MDSCs from subjects with multiple sclerosis (MS) in the active phase of disease and during remission. Patients with active MS had a significantly higher frequency and number of MDSCs in the peripheral blood compared with patients in remission and healthy controls.…”

Section: Autoimmune Disease Mdscs and Ageingmentioning

confidence: 99%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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Crucial Role of Granulocytic Myeloid-Derived Suppressor Cells in the Regulation of Central Nervous System Autoimmune Disease

Cited by 205 publications

References 67 publications

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

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