Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain

Manrique-Castano, Daniel; Dzyubenko, Egor; Borbor, Mina; Vasileiadou, Paraskevi; Kleinschnitz, Christoph; Roll, Lars; Faissner, Andréas; Hermann, Dirk M.

doi:10.1016/j.bbi.2020.10.016

Cited by 29 publications

(21 citation statements)

References 49 publications

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“…On another note, the number of infiltrating leukocytes, T cells, was shown to be increased in the ischemic brain parenchyma of Tenascin-C (TnC)-deficient mice compared with wild type mice, while the ischemic injury and neurological deficits were not affected. A mechanism was proposed in which the reduced microglia surveillance in TnC-deficient mice favors leukocyte accumulation in the ischemic brain (26). Infiltration of T cells was observed in both MCAO models at 24 h, but pMCAO resulted in much more infiltrating T cells at 5 days, which is in accordance with the fact that T lymphocytes get recruited in the later stages of ischemic brain injury (27).…”

Section: Leukocytes Lymphocytes and Macrophages In Post-ischemic Brainsupporting

confidence: 54%

Neuroinflammation in Post-Ischemic Brain

et al. 2021

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Acute neuroinflammation occurring immediately after cerebral ischemia lasts for a few days.Cytokines and chemokines promote the migration of neutrophils and macrophages to the site of inflammation in the brain. Neuroinflammation lasting 2-6 weeks is known as subacute neuroinflammation, while chronic post-ischemic inflammation lasts for months or years.Macrophages, lymphocytes, and plasma cells predominate in chronic neuroinflammation, in contrast to neutrophils that predominate in acute neuroinflammation. In addition to their harmful impact on the ischemic brain, inflammatory mediators may also exert beneficial effects in stroke recovery. The role of secondary inflammatory cells in the pathophysiology of brain ischemia are still less understood. Late post-ischemic neuroinflammation leads to secondary damage of neuronal cells. In this chapter, the role of leukocytes, T cells, T regs, B cells, neutrophils, macrophages, microglia, astrocytes, cytokines, and transcription factors in the post-ischemic brain are discussed. Post-ischemic thrombo-inflammation and the role of platelets, recently considered as a part of the innate immune system, are also addressed. The current pharmacotherapy and future strategies for the treatment of neuroinflammation in post-ischemic brain as well as the limitations of translation between preclinical and clinical studies are presented.

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Section: Leukocytes Lymphocytes and Macrophages In Post-ischemic Brainsupporting

confidence: 54%

Neuroinflammation in Post-Ischemic Brain

et al. 2021

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“…Interestingly, inhibition of hyaluronidase, the enzyme responsible for the liberation of hyaluronan fragments from the extracellular matrix, has been shown to improve the functional outcomes after ischemic stroke [ 51 ]. Expression of another extracellular matrix DAMP, tenascin C, was found to upregulate after experimental ischemic stroke, and interestingly, the knockout of tenascin C compromised the exploratory and surveillance activity of the microglia and led to the increased infiltration of peripheral leukocytes, particularly T cells [ 52 ]. In a subtype of hemorrhagic stroke, the subarachnoid hemorrhage, tenascin C has been shown to be associated with neuroinflammation, BBB disruption, neuronal apoptosis, cerebral vasospasm and neurological deficits via upregulation of MAPKs and NFκB [ 53 ].…”

Section: Means Of Interaction Between Brain and Immune Cellsmentioning

confidence: 99%

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Muhammad

Chaudhry

Kahlert

et al. 2021

Cells

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Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.

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“…These characteristics support its potential as a marker of poor prognosis, underpinned by its impact on cell motility and invasion, aberrant angiogenesis (45) and immunomodulation (31,46,47). Importantly, TnC modulates the activation state of immune cells such as macrophages and lymphocytes; this appears to be an important aspect of its contribution to both physiological tissue repair, as well as pathological conditions involving tissue remodeling (48)(49)(50).…”

Section: Physiopathological Roles Of Tnc and Their Molecular Basismentioning

confidence: 85%

Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

Albacete-Albacete¹,

Sánchez-Álvarez²,

Pozo³

2021

Front. Immunol.

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ECM composition and architecture are tightly regulated for tissue homeostasis. Different disorders have been associated to alterations in the levels of proteins such as collagens, fibronectin (FN) or tenascin-C (TnC). TnC emerges as a key regulator of multiple inflammatory processes, both during physiological tissue repair as well as pathological conditions ranging from tumor progression to cardiovascular disease. Importantly, our current understanding as to how TnC and other non-collagen ECM components are secreted has remained elusive. Extracellular vesicles (EVs) are small membrane-bound particles released to the extracellular space by most cell types, playing a key role in cell-cell communication. A broad range of cellular components can be transported by EVs (e.g. nucleic acids, lipids, signalling molecules and proteins). These cargoes can be transferred to target cells, potentially modulating their function. Recently, several extracellular matrix (ECM) proteins have been characterized as bona fide EV cargoes, exosomal secretion being particularly critical for TnC. EV-dependent ECM secretion might underpin diseases where ECM integrity is altered, establishing novel concepts in the field such as ECM nucleation over long distances, and highlighting novel opportunities for diagnostics and therapeutic intervention. Here, we review recent findings and standing questions on the molecular mechanisms governing EV–dependent ECM secretion and its potential relevance for disease, with a focus on TnC.

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Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain

Cited by 29 publications

References 49 publications

Neuroinflammation in Post-Ischemic Brain

Neuroinflammation in Post-Ischemic Brain

Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Extracellular Vesicles: An Emerging Mechanism Governing the Secretion and Biological Roles of Tenascin-C

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