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Journal article
Innate Lymphoid Cells Are the Predominant Source of IL-17A during the Early Pathogenesis of Acute Respiratory Distress Syndrome
American journal of respiratory and critical care medicine, v 193(4), pp 407-416
15 Feb 2016
PMID: 26488187
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Although IL-17A is the archetypal cytokine of T-helper 17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown.
To identify the cellular source and the role of IL-17A in the early phase of lung injury.
Lung injury was induced in wild-type (C57BL/6) and IL-17 knockout (KO) mice with aerosolized LPS (100 μg) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing RORγt, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was performed by flow cytometry.
A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared with wild-type mice. The majority of RORγt(+) cells in the mouse lung were the recently identified group 3 innate lymphoid cells (ILC3s). Detailed characterization revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in recombinase-activating gene 2 KO mice, which lack T cells but retain innate lymphoid cells. No amelioration of pathology was observed in the recombinase-activating gene 2 KO mice.
IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3s. Modulation of the activity of pILC3s may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.
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Details
- Title
- Innate Lymphoid Cells Are the Predominant Source of IL-17A during the Early Pathogenesis of Acute Respiratory Distress Syndrome
- Creators
- Roshell Muir - Queen's University BelfastMegan Osbourn - Queen's University BelfastAlice V Dubois - Queen's University BelfastEmma Doran - Queen's University BelfastDonna M Small - Queen's University BelfastAvril Monahan - Queen's University BelfastCecilia M O'KaneKatherine McAllister - Queen's University BelfastDenise C Fitzgerald - Queen's University BelfastAdrien Kissenpfennig - Queen's University BelfastDaniel F McAuley - Queen's University BelfastRebecca J Ingram - Queen's University Belfast
- Publication Details
- American journal of respiratory and critical care medicine, v 193(4), pp 407-416
- Grant note
- BB/J01026X/1 / Biotechnology and Biological Sciences Research Council
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000370392100013
- Scopus ID
- 2-s2.0-84975117326
- Other Identifier
- 991021944487204721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Critical Care Medicine
- Respiratory System