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.
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Saiwai
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumamaru
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Kazu
authors.initials: K
authors.lastname: Kobayakawa
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000950:Antigens, Ly / Q000378:metabolism*; D005260:Female; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D019707:Receptors, Chemokine / Q000276:immunology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000906:Antibodies; D000950:Antigens, Ly; C503133:Gr-1 protein, mouse; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D019707:Receptors, Chemokine