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Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition.
Pasciuto, Emanuela; Burton, Oliver T; Roca, Carlos P; Lagou, Vasiliki; Rajan, Wenson D; Theys, Tom; Mancuso, Renzo; Tito, Raul Y; Kouser, Lubna; Callaerts-Vegh, Zsuzsanna; de la Fuente, Alerie G; Prezzemolo, Teresa; Mascali, Loriana G; Brajic, Aleksandra; Whyte, Carly E; Yshii, Lidia; Martinez-Muriana, Anna; Naughton, Michelle; Young, Andrew; Moudra, Alena; Lemaitre, Pierre; Poovathingal, Suresh; Raes, Jeroen; De Strooper, Bart; Fitzgerald, Denise C; Dooley, James; Liston, Adrian.
Afiliação
  • Pasciuto E; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Burton OT; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Roca CP; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Lagou V; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Rajan WD; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Theys T; Department of Neurosurgery, UZ Leuven, Leuven 3000, Belgium.
  • Mancuso R; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Tito RY; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; VIB-KU Leuven Center for Microbiology, VIB, Leuven 3000, Belgium.
  • Kouser L; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Callaerts-Vegh Z; Department of Brain and Cognition, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • de la Fuente AG; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast BT7 1NN, UK.
  • Prezzemolo T; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Mascali LG; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Brajic A; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Whyte CE; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Yshii L; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Martinez-Muriana A; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Naughton M; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast BT7 1NN, UK.
  • Young A; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast BT7 1NN, UK.
  • Moudra A; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Lemaitre P; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
  • Poovathingal S; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium.
  • Raes J; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; VIB-KU Leuven Center for Microbiology, VIB, Leuven 3000, Belgium.
  • De Strooper B; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven-University of Leuven, Leuven 3000, Belgium; Dementia Research Institute, University College London, London WC1E 6BT, UK.
  • Fitzgerald DC; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast BT7 1NN, UK.
  • Dooley J; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
  • Liston A; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Electronic address: adrian.listo
Cell ; 182(3): 625-640.e24, 2020 08 06.
Article em En | MEDLINE | ID: mdl-32702313
The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sinapses / Encéfalo / Linfócitos T CD4-Positivos / Microglia / Feto Limite: Adult / Animals / Child / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sinapses / Encéfalo / Linfócitos T CD4-Positivos / Microglia / Feto Limite: Adult / Animals / Child / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article