Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil
Neuroinflammatory roles of central innate immunity in brain parenchyma are well-regarded in the progression of neurodegenerative disorders including Alzheimer's disease (AD), however, the roles of peripheral immunity in central nervous system (CNS) diseases are less clear. Here, we created a mi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02231/full |
| _version_ | 1819108130023276544 |
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| author | Joseph Park Sung Hoon Baik Inhee Mook-Jung Daniel Irimia Hansang Cho Hansang Cho Hansang Cho |
| author_facet | Joseph Park Sung Hoon Baik Inhee Mook-Jung Daniel Irimia Hansang Cho Hansang Cho Hansang Cho |
| author_sort | Joseph Park |
| collection | DOAJ |
| description | Neuroinflammatory roles of central innate immunity in brain parenchyma are well-regarded in the progression of neurodegenerative disorders including Alzheimer's disease (AD), however, the roles of peripheral immunity in central nervous system (CNS) diseases are less clear. Here, we created a microfluidic environment of human AD brains: microglial neuroinflammation induced by soluble amyloid-beta (Abeta), a signature molecule in AD and employed the environment to investigate the roles of neutrophils through the central-peripheral innate immunity crosstalk. We observed that soluble Abeta-activated human microglial cells produced chemoattractants for neutrophils including IL6, IL8, CCL2, CCL3/4, CCL5 and consequently induced reliable recruitment of human neutrophils. Particularly, we validated the discernable chemo-attractive roles of IL6, IL8, and CCL2 for neutrophils by interrupting the recruitment with neutralizing antibodies. Upon recruitment, microglia-neutrophils interaction results in the production of inflammatory mediators such as MIF and IL2, which are known to up-regulate neuroinflammation in AD. We envision that targeting the crosstalk between central-peripheral immune community is a potential strategy to reduce immunological burdens in other neuroinflammatory CNS diseases. |
| first_indexed | 2024-12-22T03:05:02Z |
| format | Article |
| id | doaj.art-25239d27ea3c4d96b2cd06c75825ecc7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T03:05:02Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-25239d27ea3c4d96b2cd06c75825ecc72022-12-21T18:41:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-09-011010.3389/fimmu.2019.02231480449Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in NeutrophilJoseph Park0Sung Hoon Baik1Inhee Mook-Jung2Daniel Irimia3Hansang Cho4Hansang Cho5Hansang Cho6The Nanoscale Science Program, Department of Mechanical Engineering and Engineering Science, Department of Biological Sciences, Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, United StatesDepartment of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, South KoreaDepartment of Biochemistry and Biomedical Sciences, Seoul National University, Seoul, South KoreaDepartment of Surgery, BioMEMS Resource Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United StatesThe Nanoscale Science Program, Department of Mechanical Engineering and Engineering Science, Department of Biological Sciences, Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, United StatesDepartment of Surgery, BioMEMS Resource Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United StatesDepartment of Biophysics, Institute of Quantum Biology, Sungkyunkwan University, Suwon, South KoreaNeuroinflammatory roles of central innate immunity in brain parenchyma are well-regarded in the progression of neurodegenerative disorders including Alzheimer's disease (AD), however, the roles of peripheral immunity in central nervous system (CNS) diseases are less clear. Here, we created a microfluidic environment of human AD brains: microglial neuroinflammation induced by soluble amyloid-beta (Abeta), a signature molecule in AD and employed the environment to investigate the roles of neutrophils through the central-peripheral innate immunity crosstalk. We observed that soluble Abeta-activated human microglial cells produced chemoattractants for neutrophils including IL6, IL8, CCL2, CCL3/4, CCL5 and consequently induced reliable recruitment of human neutrophils. Particularly, we validated the discernable chemo-attractive roles of IL6, IL8, and CCL2 for neutrophils by interrupting the recruitment with neutralizing antibodies. Upon recruitment, microglia-neutrophils interaction results in the production of inflammatory mediators such as MIF and IL2, which are known to up-regulate neuroinflammation in AD. We envision that targeting the crosstalk between central-peripheral immune community is a potential strategy to reduce immunological burdens in other neuroinflammatory CNS diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.02231/fullneuroinflammationneurodegenerationAlzheimer's diseasemicroglianeutrophilchemotaxis |
| spellingShingle | Joseph Park Sung Hoon Baik Inhee Mook-Jung Daniel Irimia Hansang Cho Hansang Cho Hansang Cho Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil Frontiers in Immunology neuroinflammation neurodegeneration Alzheimer's disease microglia neutrophil chemotaxis |
| title | Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil |
| title_full | Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil |
| title_fullStr | Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil |
| title_full_unstemmed | Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil |
| title_short | Mimicry of Central-Peripheral Immunity in Alzheimer's Disease and Discovery of Neurodegenerative Roles in Neutrophil |
| title_sort | mimicry of central peripheral immunity in alzheimer s disease and discovery of neurodegenerative roles in neutrophil |
| topic | neuroinflammation neurodegeneration Alzheimer's disease microglia neutrophil chemotaxis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02231/full |
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