Ly6C+Ly6G- Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury

Hirokazu Saiwai, Hiromi Kumamaru, Yasuyuki Ohkawa, Kensuke Kubota, Kazu Kobayakawa, Hisakata Yamada, Takehiko Yokomizo, Yukihide Iwamoto, Seiji Okada

研究成果: ジャーナルへの寄稿記事

55 引用 (Scopus)

抄録

Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue. Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown. In this study, we demonstrated that an initial infiltration of Ly6C+Ly6G- immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model. Complete depletion of Ly6C+Ly6G- fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes. Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome. Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery. Our findings reveal the crucial role of an Ly6C+Ly6G- fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases. Myeloid-derived suppressor cells (MDSCs) exert immunosuppressive effects in several inflammatory diseases, including cancer and autoimmune disease. We demonstrated that Ly6C+Ly6G- myeloid cells which infiltrated into injured spinal cord had a typical feature of MDSCs and played a critical role in the attenuation of acute inflammation and the subsequent tissue repair process after spinal cord injury (SCI). Our findings clarified the role of MDSCs after traumatic SCI, and suggested a potential MDSC-based therapeutic strategy for the acute phase of central nervous system injury.

元の言語英語
ページ(範囲)74-88
ページ数15
ジャーナルJournal of Neurochemistry
125
発行部数1
DOI
出版物ステータス出版済み - 4 1 2013

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Spinal Cord Injuries
Repair
Tissue
Inflammation
Neurology
Infiltration
Central Nervous System
Recovery
Tissue regeneration
Immunosuppressive Agents
Nervous System Trauma
Myeloid-Derived Suppressor Cells
Nerve Tissue
Wounds and Injuries
Acute Disease
Myeloid Cells
Autoimmune Diseases
Antibodies
Regeneration
Monocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

これを引用

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title = "Ly6C+Ly6G- Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury",
abstract = "Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue. Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown. In this study, we demonstrated that an initial infiltration of Ly6C+Ly6G- immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model. Complete depletion of Ly6C+Ly6G- fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes. Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome. Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery. Our findings reveal the crucial role of an Ly6C+Ly6G- fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases. Myeloid-derived suppressor cells (MDSCs) exert immunosuppressive effects in several inflammatory diseases, including cancer and autoimmune disease. We demonstrated that Ly6C+Ly6G- myeloid cells which infiltrated into injured spinal cord had a typical feature of MDSCs and played a critical role in the attenuation of acute inflammation and the subsequent tissue repair process after spinal cord injury (SCI). Our findings clarified the role of MDSCs after traumatic SCI, and suggested a potential MDSC-based therapeutic strategy for the acute phase of central nervous system injury.",
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AU - Saiwai, Hirokazu

AU - Kumamaru, Hiromi

AU - Ohkawa, Yasuyuki

AU - Kubota, Kensuke

AU - Kobayakawa, Kazu

AU - Yamada, Hisakata

AU - Yokomizo, Takehiko

AU - Iwamoto, Yukihide

AU - Okada, Seiji

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AB - Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue. Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown. In this study, we demonstrated that an initial infiltration of Ly6C+Ly6G- immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model. Complete depletion of Ly6C+Ly6G- fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes. Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome. Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery. Our findings reveal the crucial role of an Ly6C+Ly6G- fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases. Myeloid-derived suppressor cells (MDSCs) exert immunosuppressive effects in several inflammatory diseases, including cancer and autoimmune disease. We demonstrated that Ly6C+Ly6G- myeloid cells which infiltrated into injured spinal cord had a typical feature of MDSCs and played a critical role in the attenuation of acute inflammation and the subsequent tissue repair process after spinal cord injury (SCI). Our findings clarified the role of MDSCs after traumatic SCI, and suggested a potential MDSC-based therapeutic strategy for the acute phase of central nervous system injury.

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