Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System
Summary: Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720302904 |
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doaj-bd22cf9222c14c19a516a5d90377ff74 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Patrick Süß Alana Hoffmann Tobias Rothe Zhengyu Ouyang Wolfgang Baum Ori Staszewski Georg Schett Marco Prinz Gerhard Krönke Christopher K. Glass Jürgen Winkler Johannes C.M. Schlachetzki |
| spellingShingle |
Patrick Süß Alana Hoffmann Tobias Rothe Zhengyu Ouyang Wolfgang Baum Ori Staszewski Georg Schett Marco Prinz Gerhard Krönke Christopher K. Glass Jürgen Winkler Johannes C.M. Schlachetzki Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System Cell Reports |
| author_facet |
Patrick Süß Alana Hoffmann Tobias Rothe Zhengyu Ouyang Wolfgang Baum Ori Staszewski Georg Schett Marco Prinz Gerhard Krönke Christopher K. Glass Jürgen Winkler Johannes C.M. Schlachetzki |
| author_sort |
Patrick Süß |
| title |
Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System |
| title_short |
Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System |
| title_full |
Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System |
| title_fullStr |
Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System |
| title_full_unstemmed |
Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System |
| title_sort |
chronic peripheral inflammation causes a region-specific myeloid response in the central nervous system |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-03-01 |
| description |
Summary: Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammation. This shift in the myeloid compartment is associated with the appearance of an inflammatory myeloid subpopulation in the cortex, striatum, and thalamus accompanied by regional transcriptomic fingerprints that include induction of chemokines, complement factors, and endothelial adhesion molecules. In contrast, myeloid immune responses within the hippocampus and cerebellum are subtle or absent. Treatment with the anti-tumor necrosis factor α (anti-TNF-α) antibody infliximab ablates the region-specific inflammatory response. A region-specific myeloid cell response to chronic peripheral inflammation is observed in postmortem brains from individuals with rheumatoid arthritis. Our data suggest that chronic peripheral inflammation has heterogeneous effects on the brain, as evidenced by the spectrum of myeloid cell responses observed across brain regions. : Süß et al. find that chronic peripheral inflammation in mice affects microglia in a brain-region-specific manner, which is reversible upon treatment with a TNF-α inhibitor. Analysis of postmortem tissue suggests a similar spatial pattern of myeloid cell response in patients with rheumatoid arthritis. Keywords: chronic peripheral inflammation, CNS myeloid cells, brain regions, human rheumatoid arthritis, blood-brain barrier, microglia |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720302904 |
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doaj-bd22cf9222c14c19a516a5d90377ff742020-11-25T02:32:08ZengElsevierCell Reports2211-12472020-03-01301240824095.e6Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous SystemPatrick Süß0Alana Hoffmann1Tobias Rothe2Zhengyu Ouyang3Wolfgang Baum4Ori Staszewski5Georg Schett6Marco Prinz7Gerhard Krönke8Christopher K. Glass9Jürgen Winkler10Johannes C.M. Schlachetzki11Department of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg im Breisgau, GermanyDepartment of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Internal Medicine 3, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Deutsches Zentrum für Immuntherapie, 91054 Erlangen, GermanyDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USADepartment of Internal Medicine 3, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, GermanyInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg im Breisgau, GermanyDepartment of Internal Medicine 3, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Deutsches Zentrum für Immuntherapie, 91054 Erlangen, GermanyInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg im Breisgau, Germany; Signalling Research Centres for BIOSS and CIBSS, University of Freiburg, 79104 Freiburg im Breisgau, Germany; Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, 79104 Freiburg im Breisgau, GermanyDepartment of Internal Medicine 3, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Deutsches Zentrum für Immuntherapie, 91054 Erlangen, GermanyDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USADepartment of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, GermanyDepartment of Molecular Neurology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital Erlangen, 91054 Erlangen, Germany; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding authorSummary: Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammation. This shift in the myeloid compartment is associated with the appearance of an inflammatory myeloid subpopulation in the cortex, striatum, and thalamus accompanied by regional transcriptomic fingerprints that include induction of chemokines, complement factors, and endothelial adhesion molecules. In contrast, myeloid immune responses within the hippocampus and cerebellum are subtle or absent. Treatment with the anti-tumor necrosis factor α (anti-TNF-α) antibody infliximab ablates the region-specific inflammatory response. A region-specific myeloid cell response to chronic peripheral inflammation is observed in postmortem brains from individuals with rheumatoid arthritis. Our data suggest that chronic peripheral inflammation has heterogeneous effects on the brain, as evidenced by the spectrum of myeloid cell responses observed across brain regions. : Süß et al. find that chronic peripheral inflammation in mice affects microglia in a brain-region-specific manner, which is reversible upon treatment with a TNF-α inhibitor. Analysis of postmortem tissue suggests a similar spatial pattern of myeloid cell response in patients with rheumatoid arthritis. Keywords: chronic peripheral inflammation, CNS myeloid cells, brain regions, human rheumatoid arthritis, blood-brain barrier, microgliahttp://www.sciencedirect.com/science/article/pii/S2211124720302904 |