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CNS-localized myeloid cells capture living invading T cells during neuroinflammation

To study the role of myeloid cells in the central nervous system (CNS) in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), we used intravital microscopy, assessing local cellular interactions in vivo in EAE animals and ex vivo in orga...

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Autores principales: Wasser, Beatrice, Luchtman, Dirk, Löffel, Julian, Robohm, Kerstin, Birkner, Katharina, Stroh, Albrecht, Vogelaar, Christina Francisca, Zipp, Frauke, Bittner, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971133/
https://www.ncbi.nlm.nih.gov/pubmed/32219436
http://dx.doi.org/10.1084/jem.20190812
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author Wasser, Beatrice
Luchtman, Dirk
Löffel, Julian
Robohm, Kerstin
Birkner, Katharina
Stroh, Albrecht
Vogelaar, Christina Francisca
Zipp, Frauke
Bittner, Stefan
author_facet Wasser, Beatrice
Luchtman, Dirk
Löffel, Julian
Robohm, Kerstin
Birkner, Katharina
Stroh, Albrecht
Vogelaar, Christina Francisca
Zipp, Frauke
Bittner, Stefan
author_sort Wasser, Beatrice
collection PubMed
description To study the role of myeloid cells in the central nervous system (CNS) in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), we used intravital microscopy, assessing local cellular interactions in vivo in EAE animals and ex vivo in organotypic hippocampal slice cultures. We discovered that myeloid cells actively engulf invading living Th17 lymphocytes, a process mediated by expression of activation-dependent lectin and its T cell–binding partner, N-acetyl-D-glucosamine (GlcNAc). Stable engulfment resulted in the death of the engulfed cells, and, remarkably, enhancement of GlcNAc exposure on T cells in the CNS ameliorated clinical EAE symptoms. These findings demonstrate the ability of myeloid cells to directly react to pathogenic T cell infiltration by engulfing living T cells. Amelioration of EAE via GlcNAc treatment suggests a novel first-defense pathway of myeloid cells as an initial response to CNS invasion and demonstrates that T cell engulfment by myeloid cells can be therapeutically exploited in vivo.
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spelling pubmed-79711332021-03-26 CNS-localized myeloid cells capture living invading T cells during neuroinflammation Wasser, Beatrice Luchtman, Dirk Löffel, Julian Robohm, Kerstin Birkner, Katharina Stroh, Albrecht Vogelaar, Christina Francisca Zipp, Frauke Bittner, Stefan J Exp Med Article To study the role of myeloid cells in the central nervous system (CNS) in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), we used intravital microscopy, assessing local cellular interactions in vivo in EAE animals and ex vivo in organotypic hippocampal slice cultures. We discovered that myeloid cells actively engulf invading living Th17 lymphocytes, a process mediated by expression of activation-dependent lectin and its T cell–binding partner, N-acetyl-D-glucosamine (GlcNAc). Stable engulfment resulted in the death of the engulfed cells, and, remarkably, enhancement of GlcNAc exposure on T cells in the CNS ameliorated clinical EAE symptoms. These findings demonstrate the ability of myeloid cells to directly react to pathogenic T cell infiltration by engulfing living T cells. Amelioration of EAE via GlcNAc treatment suggests a novel first-defense pathway of myeloid cells as an initial response to CNS invasion and demonstrates that T cell engulfment by myeloid cells can be therapeutically exploited in vivo. Rockefeller University Press 2020-03-27 /pmc/articles/PMC7971133/ /pubmed/32219436 http://dx.doi.org/10.1084/jem.20190812 Text en © 2020 Wasser et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Wasser, Beatrice
Luchtman, Dirk
Löffel, Julian
Robohm, Kerstin
Birkner, Katharina
Stroh, Albrecht
Vogelaar, Christina Francisca
Zipp, Frauke
Bittner, Stefan
CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title_full CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title_fullStr CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title_full_unstemmed CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title_short CNS-localized myeloid cells capture living invading T cells during neuroinflammation
title_sort cns-localized myeloid cells capture living invading t cells during neuroinflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971133/
https://www.ncbi.nlm.nih.gov/pubmed/32219436
http://dx.doi.org/10.1084/jem.20190812
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