Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma - 27/09/17
Abstract |
Background |
The mechanism of TH2/TH17-predominant and TH2/TH17-low asthma is unknown.
Objective |
We sought to study the immune mechanism of TH2/TH17-predominant and TH2/TH17-low asthma.
Methods |
In a previously reported cohort of 60 asthmatic patients, 16 patients were immunophenotyped with TH2/TH17-predominant asthma and 22 patients with TH2/TH17-low asthma. We examined bronchoalveolar lavage (BAL) fluid leukocytes, cytokines, mediators, and epithelial cell function for these asthma subgroups.
Results |
Patients with TH2/TH17-predominant asthma had increased IL-1β, IL-6, IL-23, C3a, and serum amyloid A levels in BAL fluid, and these correlated with IL-1β and C3a levels. TH2/TH17 cells expressed higher levels of the IL-1 receptor and phospho-p38 mitogen-activated protein kinase. Anakinra, an IL-1 receptor antagonist protein, inhibited BAL TH2/TH17 cell counts. TH2/TH17-low asthma had 2 distinct subgroups: neutrophilic asthma (45%) and pauci-inflammatory asthma (55%). This contrasted with patients with TH2/TH17-predominant and TH2-predominant asthma, which included neutrophilic asthma in 6% and 0% of patients, respectively. BAL fluid neutrophils strongly correlated with BAL fluid myeloperoxidase, IL-8, IL-1α, IL-6, granulocyte colony-stimulating factor, and GM-CSF levels. Sixty percent of the patients with neutrophilic asthma had a pathogenic microorganism in BAL culture, which suggested a subclinical infection.
Conclusion |
We uncovered a critical role for the IL-1β pathway in patients with TH2/TH17-predminant asthma. A subgroup of patients with TH2/TH17-low asthma had neutrophilic asthma and increased BAL fluid IL-1α, IL-6, IL-8, granulocyte colony-stimulating factor, and GM-CSF levels. IL-1α was directly involved in IL-8 production and likely contributed to neutrophilic asthma. Sixty percent of neutrophilic patients had a subclinical infection.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Asthma endotype, TH2/TH17-predominant asthma, neutrophilic asthma, IL-1, C3a, infection
Abbreviations used : BAL, DAMP, G-CSF, IL-1R, MAPK, STAT
Plan
| Supported by National Institutes of Health grants RO1 AI091614, HL126895, AI102943, and HL126895. |
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| Disclosure of potential conflict of interest: J. T. Good receives grant support from MedImmune and the National Heart, Lung, and Blood Institute (NHLBI), payments for lectures from Merck and Genentech, and payments for educational presentations form QuantiMED. S. Groshong serves as a consultant for Veracyte and payments for educational presentations from Vindico and InterMune. M. M. Gorska receives grant support from the National Institutes of Health (NIH) and the ALA. R. J. Martin serves on the board for Genentech and BI, serves as a consultant for TEVA and AstraZeneca, receives grant support from the NHLBI and MedImmune, and received travel support from the Respiratory Effectiveness Group. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 5
P. 1548 - mai 2017 Retour au numéro
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