Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke
Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC member...
Ausführliche Beschreibung
Autor*in: |
Wang, Shuaiwei [verfasserIn] |
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E-Artikel |
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Englisch |
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2023 |
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Anmerkung: |
© The Author(s) 2023 |
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Übergeordnetes Werk: |
Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 20(2023), 1 vom: 11. Jan. |
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Übergeordnetes Werk: |
volume:20 ; year:2023 ; number:1 ; day:11 ; month:01 |
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DOI / URN: |
10.1186/s12974-023-02689-x |
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Katalog-ID: |
SPR051327368 |
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520 | |a Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. | ||
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700 | 1 | |a de Fabritus, Lauriane |4 aut | |
700 | 1 | |a Kumar, Praveen Ashok |4 aut | |
700 | 1 | |a Werner, Yves |4 aut | |
700 | 1 | |a Ma, Minglu |4 aut | |
700 | 1 | |a Li, Dan |4 aut | |
700 | 1 | |a Siret, Carole |4 aut | |
700 | 1 | |a Simic, Milesa |4 aut | |
700 | 1 | |a Li, Bin |4 aut | |
700 | 1 | |a Kerdiles, Yann M. |4 aut | |
700 | 1 | |a Hou, Lei |4 aut | |
700 | 1 | |a Stumm, Ralf |4 aut | |
700 | 1 | |a van de Pavert, Serge A. |4 aut | |
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10.1186/s12974-023-02689-x doi (DE-627)SPR051327368 (SPR)s12974-023-02689-x-e DE-627 ger DE-627 rakwb eng Wang, Shuaiwei verfasserin aut Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 de Fabritus, Lauriane aut Kumar, Praveen Ashok aut Werner, Yves aut Ma, Minglu aut Li, Dan aut Siret, Carole aut Simic, Milesa aut Li, Bin aut Kerdiles, Yann M. aut Hou, Lei aut Stumm, Ralf aut van de Pavert, Serge A. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 11. Jan. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12974-023-02689-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 20 2023 1 11 01 |
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10.1186/s12974-023-02689-x doi (DE-627)SPR051327368 (SPR)s12974-023-02689-x-e DE-627 ger DE-627 rakwb eng Wang, Shuaiwei verfasserin aut Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 de Fabritus, Lauriane aut Kumar, Praveen Ashok aut Werner, Yves aut Ma, Minglu aut Li, Dan aut Siret, Carole aut Simic, Milesa aut Li, Bin aut Kerdiles, Yann M. aut Hou, Lei aut Stumm, Ralf aut van de Pavert, Serge A. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 11. Jan. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12974-023-02689-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 20 2023 1 11 01 |
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10.1186/s12974-023-02689-x doi (DE-627)SPR051327368 (SPR)s12974-023-02689-x-e DE-627 ger DE-627 rakwb eng Wang, Shuaiwei verfasserin aut Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 de Fabritus, Lauriane aut Kumar, Praveen Ashok aut Werner, Yves aut Ma, Minglu aut Li, Dan aut Siret, Carole aut Simic, Milesa aut Li, Bin aut Kerdiles, Yann M. aut Hou, Lei aut Stumm, Ralf aut van de Pavert, Serge A. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 11. Jan. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12974-023-02689-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 20 2023 1 11 01 |
allfieldsGer |
10.1186/s12974-023-02689-x doi (DE-627)SPR051327368 (SPR)s12974-023-02689-x-e DE-627 ger DE-627 rakwb eng Wang, Shuaiwei verfasserin aut Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 de Fabritus, Lauriane aut Kumar, Praveen Ashok aut Werner, Yves aut Ma, Minglu aut Li, Dan aut Siret, Carole aut Simic, Milesa aut Li, Bin aut Kerdiles, Yann M. aut Hou, Lei aut Stumm, Ralf aut van de Pavert, Serge A. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 11. Jan. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12974-023-02689-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 20 2023 1 11 01 |
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10.1186/s12974-023-02689-x doi (DE-627)SPR051327368 (SPR)s12974-023-02689-x-e DE-627 ger DE-627 rakwb eng Wang, Shuaiwei verfasserin aut Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 de Fabritus, Lauriane aut Kumar, Praveen Ashok aut Werner, Yves aut Ma, Minglu aut Li, Dan aut Siret, Carole aut Simic, Milesa aut Li, Bin aut Kerdiles, Yann M. aut Hou, Lei aut Stumm, Ralf aut van de Pavert, Serge A. aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 11. Jan. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:11 month:01 https://dx.doi.org/10.1186/s12974-023-02689-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 20 2023 1 11 01 |
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Wang, Shuaiwei misc NK cells misc ILC1 misc Photothrombotic stroke misc CNS misc Cdh5 misc CXCR4 misc Blood–brain barrier misc Whole mount imaging misc Flow cytometry misc Beam-walk sensorimotor test Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke |
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Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke NK cells (dpeaa)DE-He213 ILC1 (dpeaa)DE-He213 Photothrombotic stroke (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Cdh5 (dpeaa)DE-He213 CXCR4 (dpeaa)DE-He213 Blood–brain barrier (dpeaa)DE-He213 Whole mount imaging (dpeaa)DE-He213 Flow cytometry (dpeaa)DE-He213 Beam-walk sensorimotor test (dpeaa)DE-He213 |
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Wang, Shuaiwei de Fabritus, Lauriane Kumar, Praveen Ashok Werner, Yves Ma, Minglu Li, Dan Siret, Carole Simic, Milesa Li, Bin Kerdiles, Yann M. Hou, Lei Stumm, Ralf van de Pavert, Serge A. |
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title_sort |
brain endothelial cxcl12 attracts protective natural killer cells during ischemic stroke |
title_auth |
Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke |
abstract |
Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. © The Author(s) 2023 |
abstractGer |
Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. © The Author(s) 2023 |
abstract_unstemmed |
Background The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too. Therefore, we studied the presence of all ILC members within the central nervous system and after ischemic brain insult. Methods We used the photothrombotic ischemic lesion method to induce ischemic lesions within the mouse brain. Using whole-mount immunofluorescence imaging, we established that the ILCs were present at the rim of the lesion. We quantified the increase of all ILC members at different time-points after the ischemic lesion induction by flow cytometry. Their migration route via chemokine CXCL12 was studied by using different genetic mouse models, in which we induced deletion of Cxcl12 within the blood–brain barrier endothelium, or its receptor, Cxcr4, in the ILCs. The functional role of the ILCs was subsequently established using the beam-walk sensorimotor test. Results Here, we report that ILCs are not resident within the mouse brain parenchyma during steady-state conditions, but are attracted towards the ischemic stroke. Specifically, we identify NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that CXCL12 expressed at the blood–brain barrier is essential for NK cells and $ NKp46^{+} $ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevents NK cells from entering the infarct area. Lack of NK cell migration results in a higher neurological deficit in the beam-walk sensorimotor test. Conclusions This study establishes the lack of ILCs in the mouse central nervous system at steady-state and their migration towards an ischemic brain lesion. Our data show a role for blood–brain barrier-derived CXCL12 in attracting protective NK cells to ischemic brain lesions and identifies a new CXCL12/CXCR4-mediated component of the innate immune response to stroke. © The Author(s) 2023 |
collection_details |
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Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke |
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de Fabritus, Lauriane Kumar, Praveen Ashok Werner, Yves Ma, Minglu Li, Dan Siret, Carole Simic, Milesa Li, Bin Kerdiles, Yann M. Hou, Lei Stumm, Ralf van de Pavert, Serge A. |
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de Fabritus, Lauriane Kumar, Praveen Ashok Werner, Yves Ma, Minglu Li, Dan Siret, Carole Simic, Milesa Li, Bin Kerdiles, Yann M. Hou, Lei Stumm, Ralf van de Pavert, Serge A. |
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