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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
  • Hardy Kornfeld
  • Lindsy Forbess
  • Swamy Venuturupalli
  • Mariko Ishimori
  • Daniel Wallace
  • Michael H. Weisman
  • Caroline A. Jefferies
Organisations
External organisations
  • Royal College of Surgeons in Ireland
  • Cedars-Sinai Medical Center
  • Beaumont Hospital, Dublin
  • St Vincent's University Hospital
  • China-Japan Friendship Hospital
  • University of Massachusetts
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Respiratory Medicine and Allergy

Keywords

  • Autoimmunity, Chemokines, Immunology, Lupus, Neutrophils
Original languageEnglish
JournalJCI Insight
Volume3
Issue number15
Publication statusPublished - 2018 Aug 9
Publication categoryResearch
Peer-reviewedYes