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ludc webb

Harry Björkbacka

Researcher

ludc webb

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation

Author

  • Siobhan Smith
  • Pei Wen Wu
  • Jane J. Seo
  • Thilini Fernando
  • Mengyao Jin
  • Jorge Contreras
  • Erica N. Montano
  • Joan Ní Gabhann
  • Kyle Cunningham
  • Amro Widaa
  • Eoghan M. McCarthy
  • Eamonn S. Molloy
  • Grainne Kearns
  • Conor C. Murphy
  • Weiping Kong
  • Harry Björkbacka
  • Hardy Kornfeld
  • Lindsy Forbess
  • Swamy Venuturupalli
  • Mariko Ishimori
  • Daniel Wallace
  • Michael H. Weisman
  • Caroline A. Jefferies

Summary, in English

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2018-08-09

Language

English

Publication/Series

JCI Insight

Volume

3

Issue

15

Document type

Journal article

Publisher

The American Society for Clinical Investigation

Topic

  • Respiratory Medicine and Allergy

Keywords

  • Autoimmunity
  • Chemokines
  • Immunology
  • Lupus
  • Neutrophils

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 2379-3708