Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation

Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limit...
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Autor*in:	Mathias Linnerbauer [verfasserIn] Lena Lößlein [verfasserIn] Daniel Farrenkopf [verfasserIn] Oliver Vandrey [verfasserIn] Thanos Tsaktanis [verfasserIn] Ulrike Naumann [verfasserIn] Veit Rothhammer [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	astrocytes multiple sclerosis autoimmunity CNS inflammation protective

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 12(2022)
Übergeordnetes Werk:	volume:12 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2021.800128

Katalog-ID:	DOAJ019575211

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520			\|a Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited.
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allfields	10.3389/fimmu.2021.800128 doi (DE-627)DOAJ019575211 (DE-599)DOAJ55ac31aea3af4211b4859903a6fdc530 DE-627 ger DE-627 rakwb eng RC581-607 Mathias Linnerbauer verfasserin aut Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited. astrocytes multiple sclerosis autoimmunity CNS inflammation protective Immunologic diseases. Allergy Lena Lößlein verfasserin aut Daniel Farrenkopf verfasserin aut Oliver Vandrey verfasserin aut Thanos Tsaktanis verfasserin aut Ulrike Naumann verfasserin aut Veit Rothhammer verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2022 https://doi.org/10.3389/fimmu.2021.800128 kostenfrei https://doaj.org/article/55ac31aea3af4211b4859903a6fdc530 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.800128/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
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allfieldsSound	10.3389/fimmu.2021.800128 doi (DE-627)DOAJ019575211 (DE-599)DOAJ55ac31aea3af4211b4859903a6fdc530 DE-627 ger DE-627 rakwb eng RC581-607 Mathias Linnerbauer verfasserin aut Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited. astrocytes multiple sclerosis autoimmunity CNS inflammation protective Immunologic diseases. Allergy Lena Lößlein verfasserin aut Daniel Farrenkopf verfasserin aut Oliver Vandrey verfasserin aut Thanos Tsaktanis verfasserin aut Ulrike Naumann verfasserin aut Veit Rothhammer verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2022 https://doi.org/10.3389/fimmu.2021.800128 kostenfrei https://doaj.org/article/55ac31aea3af4211b4859903a6fdc530 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.800128/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2022
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container_title	Frontiers in Immunology
authorswithroles_txt_mv	Mathias Linnerbauer @@aut@@ Lena Lößlein @@aut@@ Daniel Farrenkopf @@aut@@ Oliver Vandrey @@aut@@ Thanos Tsaktanis @@aut@@ Ulrike Naumann @@aut@@ Veit Rothhammer @@aut@@
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callnumber-first	R - Medicine
author	Mathias Linnerbauer
spellingShingle	Mathias Linnerbauer misc RC581-607 misc astrocytes misc multiple sclerosis misc autoimmunity misc CNS inflammation misc protective misc Immunologic diseases. Allergy Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation
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topic_title	RC581-607 Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation astrocytes multiple sclerosis autoimmunity CNS inflammation protective
topic	misc RC581-607 misc astrocytes misc multiple sclerosis misc autoimmunity misc CNS inflammation misc protective misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc astrocytes misc multiple sclerosis misc autoimmunity misc CNS inflammation misc protective misc Immunologic diseases. Allergy
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title	Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation
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title_full	Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation
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title_sort	astrocyte-derived pleiotrophin mitigates late-stage autoimmune cns inflammation
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title_auth	Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation
abstract	Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited.
abstractGer	Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited.
abstract_unstemmed	Astrocytes are the most abundant glial cells in the central nervous system (CNS) with the capacity to sense and react to injury and inflammatory events. While it has been widely documented that astrocytes can exert tissue-degenerative functions, less is known about their protective and disease-limiting roles. Here, we report the upregulation of pleiotrophin (PTN) by mouse and human astrocytes in multiple sclerosis (MS) and its preclinical model experimental autoimmune encephalomyelitis (EAE). Using CRISPR-Cas9-based genetic perturbation systems, we demonstrate in vivo that astrocyte-derived PTN is critical for the recovery phase of EAE and limits chronic CNS inflammation. PTN reduces pro-inflammatory signaling in astrocytes and microglia and promotes neuronal survival following inflammatory challenge. Finally, we show that intranasal administration of PTN during the late phase of EAE successfully reduces disease severity, making it a potential therapeutic candidate for the treatment of progressive MS, for which existing therapies are limited.
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title_short	Astrocyte-Derived Pleiotrophin Mitigates Late-Stage Autoimmune CNS Inflammation
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