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Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.
Kim, Jennifer E; Lee, Ryan P; Yazigi, Eli; Atta, Lyla; Feghali, James; Pant, Ayush; Jain, Aanchal; Levitan, Idan; Kim, Eileen; Patel, Kisha; Kannapadi, Nivedha; Shah, Pavan; Bibic, Adnan; Hou, Zhipeng; Caplan, Justin M; Gonzalez, L Fernando; Huang, Judy; Xu, Risheng; Fan, Jean; Tyler, Betty; Brem, Henry; Boussiotis, Vassiliki A; Jantzie, Lauren; Robinson, Shenandoah; Koehler, Raymond C; Lim, Michael; Tamargo, Rafael J; Jackson, Christopher M.
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  • Kim JE; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Lee RP; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Yazigi E; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Atta L; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, the United States of America; Center for Computational Biology, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, the United States of America; Medical Scientist Training Program, Johns Hopkins Unive
  • Feghali J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Pant A; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America; Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Jain A; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Levitan I; Department of Neurosurgery, Rabin Medical Center, Sackler Medical School, Petah Tikva, Israel.
  • Kim E; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Patel K; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Kannapadi N; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Shah P; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Bibic A; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, the United States of America; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Hou Z; Department of Radiology, School of Medicine, Johns Hopkins University, Baltimore, MD, the United States of America.
  • Caplan JM; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Gonzalez LF; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Huang J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Xu R; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Fan J; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, the United States of America.
  • Tyler B; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Brem H; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Boussiotis VA; Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, the United States of America.
  • Jantzie L; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America; Departments of Pediatrics, Johns Hopkins University School of Medicine, Maryland, the United States of America; Kennedy Krieger Institute, Maryland, the United States of America; Dep
  • Robinson S; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America; Departments of Pediatrics, Johns Hopkins University School of Medicine, Maryland, the United States of America; Kennedy Krieger Institute, Maryland, the United States of America; Dep
  • Koehler RC; Departments of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, the United States of America.
  • Lim M; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, the United States of America.
  • Tamargo RJ; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America.
  • Jackson CM; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, the United States of America. Electronic address: cjacks53@jhmi.edu.
Brain Behav Immun ; 116: 160-174, 2024 02.
Article en En | MEDLINE | ID: mdl-38070624
ABSTRACT
Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Edema Encefálico / Accidente Cerebrovascular Isquémico Límite: Animals / Humans Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article
Texto completo
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PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Edema Encefálico / Accidente Cerebrovascular Isquémico Límite: Animals / Humans Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article