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      Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation

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          Abstract

          Astrocytes have many functions in the central nervous system (CNS). They support differentiation and homeostasis of neurons and influence synaptic activity. They are responsible for formation of the blood-brain barrier (BBB) and make up the glia limitans. Here, we review their contribution to neuroimmune interactions and in particular to those induced by the invasion of activated T cells. We discuss the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of T-cell responses within the CNS. Depending on the microenvironment, they may become potent antigen-presenting cells for T cells and they may contribute to inflammatory processes. They are also able to abrogate or reprogram T-cell responses by inducing apoptosis or secreting inhibitory mediators. We consider apparently contradictory functions of astrocytes in health and disease, particularly in their interaction with lymphocytes, which may either aggravate or suppress neuroinflammation.

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          Most cited references190

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          Control of synaptic strength by glial TNFalpha.

          Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.
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            Microglia: a sensor for pathological events in the CNS.

            The most characteristic feature of microglial cells is their rapid activation in response to even minor pathological changes in the CNS. Microglia activation is a key factor in the defence of the neural parenchyma against infectious diseases, inflammation, trauma, ischaemia, brain tumours and neurodegeneration. Microglia activation occurs as a graded response in vivo. The transformation of microglia into potentially cytotoxic cells is under strict control and occurs mainly in response to neuronal or terminal degeneration, or both. Activated microglia are mainly scavenger cells but also perform various other functions in tissue repair and neural regeneration. They form a network of immune alert resident macrophages with a capacity for immune surveillance and control. Activated microglia can destroy invading micro-organisms, remove potentially deleterious debris, promote tissue repair by secreting growth factors and thus facilitate the return to tissue homeostasis. An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.
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              GLIA: listening and talking to the synapse.

              P G Haydon (2001)
              Glial cells are emerging from the background to become more prominent in our thinking about integration in the nervous system. Given that glial cells associated with synapses integrate neuronal inputs and can release transmitters that modulate synaptic activity, it is time to rethink our understanding of the wiring diagram of the nervous system. It is no longer appropriate to consider solely neuron-neuron connections; we also need to develop a view of the intricate web of active connections among glial cells, and between glia and neurons. Without such a view, it might be impossible to decode the language of the brain.
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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2013
                20 August 2013
                : 2013
                : 320519
                Affiliations
                1Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
                2Division of Infection and Immunity, University College London, Cruciform Building, Gower Street, London WC1 6BT, UK
                3Experimental Pediatrics, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany
                Author notes
                *Monika C. Brunner-Weinzierl: monika.brunner-weinzierl@ 123456med.ovgu.de

                Academic Editor: Jonathan P. Godbout

                Author information
                http://orcid.org/0000-0003-2248-5793
                Article
                10.1155/2013/320519
                3760105
                24023412
                22eb65ce-9328-41b4-91e0-225cab1bda70
                Copyright © 2013 Ulrike Gimsa et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 February 2013
                : 9 July 2013
                Categories
                Review Article

                Immunology
                Immunology

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