36
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases

      research-article
      ,
      Journal of Neuroinflammation
      BioMed Central
      Neuroinflammation, Neurodegenerative disorders, Microglia, CD4+ T-cells

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Neuroinflammation is involved in several neurodegenerative disorders and emerging evidence indicates that it constitutes a critical process that is required for the progression of neurodegeneration. Microglial activation constitutes a central event in neuroinflammation. Furthermore, microglia can not only be activated with an inflammatory and neurotoxic phenotype (M1-like phenotype), but they also can acquire a neurosupportive functional phenotype (M2-like phenotype) characterised by the production of anti-inflammatory mediators and neurotrophic factors. Importantly, during the past decade, several studies have shown that CD4 + T-cells infiltrate the central nervous system (CNS) in many neurodegenerative disorders, in which their participation has a critical influence on the outcome of microglial activation and consequent neurodegeneration. In this review, we focus on the analysis of the interplay of the different sub-populations of CD4 + T-cells infiltrating the CNS and how they participate in regulating the outcome of neuroinflammation and neurodegeneration in the context of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis. In this regard, encephalitogenic inflammatory CD4 + T-cells, such as Th1, Th17, GM-CSF-producer CD4 + T-cells and γδT-cells, strongly contribute to chronic neuroinflammation, thus perpetuating neurodegenerative processes. In contrast, encephalitogenic or meningeal Tregs and Th2 cells decrease inflammatory functions in microglial cells and promote a neurosupportive microenvironment. Moreover, whereas some neurodegenerative disorders such as multiple sclerosis, Parkinson’s disease and Alzheimer’s disease involve the participation of inflammatory CD4 + T-cells 'naturally', the physiopathology of other neurodegenerative diseases, such as amyotrophic lateral sclerosis, is associated with the participation of anti-inflammatory CD4 + T-cells that delay the neurodegenerative process. Thus, current evidence supports the hypothesis that the involvement of CD4 + T-cells against CNS antigens constitutes a key component in regulating the progression of the neurodegenerative process.

          Related collections

          Most cited references67

          • Record: found
          • Abstract: found
          • Article: not found

          Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.

          Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

            Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.

              Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.
                Bookmark

                Author and article information

                Contributors
                h.gonzalez.v10@gmail.com
                rodrigo.pacheco@cienciavida.cl
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central (London )
                1742-2094
                2 December 2014
                2 December 2014
                2014
                : 11
                : 1
                : 201
                Affiliations
                [ ]Laboratory of Neuroimmunology, Fundación Ciencia & Vida, Avenida Zañartu #1482, Ñuñoa 7780272 Santiago, Chile
                [ ]Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andrés Bello, 8370146 Santiago, Chile
                Article
                201
                10.1186/s12974-014-0201-8
                4258012
                25441979
                140ee47f-120e-4468-9d8e-445a717fc8d3
                © González and Pacheco; licensee BioMed Central Ltd. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 September 2014
                : 12 November 2014
                Categories
                Review
                Custom metadata
                © The Author(s) 2014

                Neurosciences
                neuroinflammation,neurodegenerative disorders,microglia,cd4+ t-cells
                Neurosciences
                neuroinflammation, neurodegenerative disorders, microglia, cd4+ t-cells

                Comments

                Comment on this article