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Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome.
Tamura, Tomoyoshi; Cheng, Changde; Chen, Wenan; Merriam, Louis T; Athar, Humra; Kim, Yaunghyun H; Manandhar, Reshmi; Amir Sheikh, Muhammad Dawood; Pinilla-Vera, Mayra; Varon, Jack; Hou, Peter C; Lawler, Patrick R; Oldham, William M; Seethala, Raghu R; Tesfaigzi, Yohannes; Weissman, Alexandra J; Baron, Rebecca M; Ichinose, Fumito; Berg, Katherine M; Bohula, Erin A; Morrow, David A; Chen, Xiang; Kim, Edy Y.
Affiliation
  • Tamura T; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Cheng C; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Chen W; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Merriam LT; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Athar H; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Kim YH; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Manandhar R; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Amir Sheikh MD; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Pinilla-Vera M; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Varon J; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Hou PC; Harvard Medical School, Boston, MA 02115, USA; Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Lawler PR; Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, ON M5G 2N2, Canada; McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
  • Oldham WM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Seethala RR; Harvard Medical School, Boston, MA 02115, USA; Division of Emergency Critical Care Medicine, Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Tesfaigzi Y; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Weissman AJ; Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Baron RM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Ichinose F; Harvard Medical School, Boston, MA 02115, USA; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Berg KM; Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Bohula EA; Harvard Medical School, Boston, MA 02115, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Morrow DA; Harvard Medical School, Boston, MA 02115, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Chen X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: xiang.chen@stjude.org.
  • Kim EY; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: ekim11@bwh.harvard.edu.
Med ; 4(7): 432-456.e6, 2023 Jul 14.
Article in En | MEDLINE | ID: mdl-37257452
ABSTRACT

BACKGROUND:

Most patients hospitalized after cardiac arrest (CA) die because of neurological injury. The systemic inflammatory response after CA is associated with neurological injury and mortality but remains poorly defined.

METHODS:

We determine the innate immune network induced by clinical CA at single-cell resolution.

FINDINGS:

Immune cell states diverge as early as 6 h post-CA between patients with good or poor neurological outcomes 30 days after CA. Nectin-2+ monocyte and Tim-3+ natural killer (NK) cell subpopulations are associated with poor outcomes, and interactome analysis highlights their crosstalk via cytokines and immune checkpoints. Ex vivo studies of peripheral blood cells from CA patients demonstrate that immune checkpoints are a compensatory mechanism against inflammation after CA. Interferon γ (IFNγ)/interleukin-10 (IL-10) induced Nectin-2 on monocytes; in a negative feedback loop, Nectin-2 suppresses IFNγ production by NK cells.

CONCLUSIONS:

The initial hours after CA may represent a window for therapeutic intervention in the resolution of inflammation via immune checkpoints.

FUNDING:

This work was supported by funding from the American Heart Association, Brigham and Women's Hospital Department of Medicine, the Evergreen Innovation Fund, and the National Institutes of Health.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cytokines / Transcriptome Limits: Female / Humans Country/Region as subject: America do norte Language: En Journal: Med Year: 2023 Document type: Article Affiliation country: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cytokines / Transcriptome Limits: Female / Humans Country/Region as subject: America do norte Language: En Journal: Med Year: 2023 Document type: Article Affiliation country: United States