Journal article
Unexpected Role for Adaptive alpha beta Th17 Cells in Acute Respiratory Distress Syndrome
The Journal of immunology (1950), v 195(1), pp 87-95
01 Jul 2015
PMID: 26002979
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. In this study, we report that expansion of Ag-specific alpha beta Th17 cells contributes to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability. Mice with a highly restrictive defect in Ag-specific alpha beta Th17 cells were protected from experimental ARDS induced by a single dose of endotracheal LPS. Loss of IL-17 receptor C or Ab blockade of IL-17A was similarly protective, further suggesting that IL-17A released by these cells was responsible for this effect. LPS induced a rapid and specific clonal expansion of alpha beta Th17 cells in the lung, as determined by deep sequencing of the hypervariable CD3R beta VJ region of the TCR. Our findings could be relevant to ARDS in humans, because we found significant elevation of IL-17A in bronchoalveolar lavage fluid from patients with ARDS, and rIL-17A directly increased permeability across cultured human alveolar epithelial monolayers. These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that alpha beta Th17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease.
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Details
- Title
- Unexpected Role for Adaptive alpha beta Th17 Cells in Acute Respiratory Distress Syndrome
- Creators
- John T. Li - University of California, San FranciscoAndrew C. Melton - University of California, San FranciscoGeorge Su - San Francisco General HospitalDavid E. Hamm - Adaptive BiotechnologiesMichael LaFemina - San Francisco VA Medical CenterJames Howard - UCSF Benioff Children's HospitalXiaohui Fang - Pacific Research InstituteSudarshan Bhat - University of California, BerkeleyKieu-My Huynh - University of California, San FranciscoCecilia M. O'Kane - Queens UniversityRebecca J. Ingram - Queen's University BelfastRoshell R. Muir - Queen's University BelfastDaniel F. McAuley - Queen's University BelfastMichael A. Matthay - Pacific Research InstituteDean Sheppard - University of California, San Francisco
- Publication Details
- The Journal of immunology (1950), v 195(1), pp 87-95
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 9
- Grant note
- CDV/3778/08 / Public Health Agency U19AI077439 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Health and Social Care Research and Development Division, Public Health Agency Northern Ireland R37HL53949; K08HL111208; R37HL51856 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R37HL051856 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000358064500015
- Scopus ID
- 2-s2.0-84932169598
- Other Identifier
- 991021944022004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology