The presence and suppressive activity of myeloid-derived suppressor cells are potentiated after interferon-β treatment in a murine model of multiple sclerosis

Melero-Jerez, Carolina; Suardíaz, Margarita; Lebrón-Galán, Rafael; Marín-Bañasco, Carmen; Oliver-Martos, Begoña; Machín-Díaz, Isabel; Fernández, Óscar; Castro, Fernando de; Clemente, Diego

doi:10.1016/j.nbd.2019.02.014

Cited by 35 publications

(47 citation statements)

References 73 publications

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“…1C and D). In addition, severity index ( [25]), was signi cantly lower in tPA −/− than in WT mice (tPA −/− severity index: 0.3440 ± 0.4986 vs WT: 0.6652 ± 0.5522, P = 0.0075, Fig. 1E).…”

Section: Resultsmentioning

confidence: 91%

“…Then, cells were harvested by centrifugation (2000 rpm, 10 min, RT), washed in PBS and stained for the ow cytometry assay. To study the effect of tPA during MOG-induced stimulation, splenocytes were obtained from MOG-immunized C57BL6/J mice at the peak of clinical score (≥ 3), as described previously [25,26] and were plated in IMDM, (BioWest, Nuaillé, France) supplemented with 2 mM L-glutamine, 1% P/S, 10% FBS (Gibco) and 50 µM β-mercaptoethanol, in U-bottom 96-well plates at a density of 2 × 10 5 cells. Splenocytes were exposed to 2 µM Tag-it Violet™ Proliferation and Cell Tracking Dye (Biolegend) diluted in PBS supplemented with 0.1% BSA at 37ºC with shaking for 20 min, protected from light.…”

Section: Methodsmentioning

confidence: 99%

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Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses

Hélie

Toledano

Miralles

et al. 2020

Preprint

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Background Tissue plasminogen activator (tPA) is a serine protease involved in fibrinolysis. It is released by endothelial cells, but also expressed by neurons and glial cells in the central nervous system (CNS). Interestingly, this enzyme also contributes to pathological processes in the CNS such as neuroinflammation by activating microglia and increasing blood-brain-barrier permeability. Nevertheless, its role in the control of adaptive and innate immune response remains poorly understood. Methods tPA effects on myeloid and lymphoid cell response were studied in vivo in the mouse model of multiple sclerosis experimental autoimmune encephalomyelitis and in vitro in splenocytes. Results tPA−/− animals exhibited less severe experimental autoimmune encephalomyelitis than their wild type counterparts. This was accompanied by a reduction in both lymphoid and myeloid cell populations in the spinal cord parenchyma. In parallel, tPA increased T cell activation and proliferation, as well as cytokine production by a protease-dependent mechanism and via plasmin generation. In addition, tPA raised the expression of MHC-II and the co-stimulatory molecule CD80 and CD86 at the surface of dendritic cells and macrophages by an effect dependent of the proteolytic activity of tPA and of the activation of epidermal growth factor receptor. Conclusions Our study provides new insights into the mechanisms responsible for the harmful functions of tPA in multiple sclerosis and its animal models: tPA promotes the proliferation and activation of both lymphoid and myeloid populations by distinct, though complementary, mechanisms.

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Section: Resultsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses

Hélie

Toledano

Miralles

et al. 2020

Preprint

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“…IFNβ treatment ameliorates EAE, and lack of IFNβ or selective defect of its receptor IFNAR1 on myeloid cells results in exacerbation of EAE. [40][41][42] Microglia are a major source of IFNβ in EAE, and infiltrating myeloid cells also contribute to CNS-endogenous IFNβ. 37,42 Peripheral treatment of mice with IFNβ at the onset of disease enhanced the presence of EAE-suppressive MDSCs in spinal cord.…”

Section: F I G U R Ementioning

confidence: 99%

“…Observation that G/PMN‐MRCs suppression was IFNα receptor (IFNAR, receptor for type I IFNs)‐dependent resonates with the known role for type I IFNs in EAE. IFNβ treatment ameliorates EAE, and lack of IFNβ or selective defect of its receptor IFNAR1 on myeloid cells results in exacerbation of EAE 40‐42 . Microglia are a major source of IFNβ in EAE, and infiltrating myeloid cells also contribute to CNS‐endogenous IFNβ 37,42 .…”

Section: Myeloid Regulatory Cells In Ms and Eaementioning

confidence: 99%

Protective roles for myeloid cells in neuroinflammation

et al. 2020

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Myeloid cells represent the major cellular component of innate immune responses. Myeloid cells include monocytes and macrophages, granulocytes (neutrophils, basophils and eosinophils) and dendritic cells (DC). The role of myeloid cells has been broadly described both in physiological and in pathological conditions. All tissues or organs are equipped with resident myeloid cells, such as parenchymal microglia in the brain, which contribute to maintaining homeostasis. Moreover, in case of infection or tissue damage, other myeloid cells such as monocytes or granulocytes (especially neutrophils) can be recruited from the circulation, at first to promote inflammation and later to participate in repair and regeneration. This review aims to address the regulatory roles of myeloid cells in inflammatory diseases of the central nervous system (CNS), with a particular focus on recent work showing induction of suppressive function via stimulation of innate signalling in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE).

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“…In patients suffering from a MS relapse, the number of circulating MDSCs is increased. Interferon-β, a first-line treatment for MS, could act among many mechanisms by enhancing MDSC activity [83]. Studies are showing both increased and decreased frequencies of MDSCs in MS [81].…”

Section: Contribution Of Immune Network To Ms Resolutionmentioning

confidence: 99%

Resolution of inflammation during multiple sclerosis

2019

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Multiple sclerosis (MS) is a frequent autoimmune demyelinating disease of the central nervous system (CNS). There are three clinical forms described: relapsing-remitting multiple sclerosis (RRMS), the most common initial presentation (85%) among which, if not treated, about half will transform, into the secondary progressive multiple sclerosis (SPMS) and the primary progressive MS (PPMS) (15%) that is directly progressive without superimposed clinical relapses. Inflammation is present in all subsets of MS. The relapsing/ remitting form could represent itself a particular interest for the study of inflammation resolution even though it remains incomplete in MS. Successful resolution of acute inflammation is a highly regulated process and dependent on mechanisms engaged early in the inflammatory response that are scarcely studied in MS. Moreover, recent classes of disease-modifying treatment (DMTs) that are effective against RRMS act by re-establishing the inflammatory imbalance, taking advantage of the pre-existing endogenous suppressor. In this review, we will discuss the active role of regulatory immune cells in inflammation resolution as well as the role of tissue and non-hematopoietic cells as contributors to inflammation resolution. Finally, we will explore how DMTs, more specifically induction therapies, impact the resolution of inflammation during MS.

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The presence and suppressive activity of myeloid-derived suppressor cells are potentiated after interferon-β treatment in a murine model of multiple sclerosis

Cited by 35 publications

References 73 publications

Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses

Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses

Protective roles for myeloid cells in neuroinflammation

Resolution of inflammation during multiple sclerosis

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