Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis

Sheng Wang; Yang Yang; Andrew Suen; Jing Zhu; Brittney Williams; Jiang Hu; Fengqian Chen; Rosemary Kozar; Shiqian Shen; Ziyi Li; Anjana Jeyaram; Steven M. Jay; Lin Zou; Wei Chao

iScience (Dec 2021)

Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis

Sheng Wang,
Yang Yang,
Andrew Suen,
Jing Zhu,
Brittney Williams,
Jiang Hu,
Fengqian Chen,
Rosemary Kozar,
Shiqian Shen,
Ziyi Li,
Anjana Jeyaram,
Steven M. Jay,
Lin Zou,
Wei Chao

Affiliations

Sheng Wang: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Yang Yang: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Diagnostic Ultrasound, The Second Xiangya Hospital, Central South University, Changsha, China
Andrew Suen: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, Halifax, NS, Canada
Jing Zhu: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Brittney Williams: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Jiang Hu: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Fengqian Chen: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Rosemary Kozar: Program in Trauma & Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Shiqian Shen: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Ziyi Li: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Anjana Jeyaram: Fischell Department of Bioengineering, A James Clark School of Engineering, University of Maryland, College Park, MD 20742, USA
Steven M. Jay: Fischell Department of Bioengineering, A James Clark School of Engineering, University of Maryland, College Park, MD 20742, USA
Lin Zou: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
Wei Chao: Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author

Journal volume & issue: Vol. 24, no. 12
p. 103441

Abstract

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Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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