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Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma
Open accessAbstract
Background Th2 cells can further differentiate into dual positive Th2/Th17 cells. The presence of dual positive Th2/Th17 cells in the airways and its impact on asthma severity are unknown. Objective To study dual positive Th2/Th17 cells in bronchoalveolar lavage (BAL) from asthmatic patients, examine their response to glucocorticoids, and define their relevance for disease severity. Methods Bronchoscopy and lavage were performed on 52 asthmatic patients and 25 disease controls. Th2 and Th2/Th17 cells were analyzed by multi-color flow cytometry and confocal immunofluorescence microscopy. Cytokines were assayed by ELISA. Results Dual positive Th2/Th17 cells were present at a higher frequency in BAL from asthmatic patients as compared to disease controls. High-level IL4 production was typically accompanied by high-level IL17 production and co-expression of GATA3 and RORγT. Increased presence of Th2/Th17 cells was associated with elevated IL17 in the lavage fluid. Th2/Th17 cells and IL17 correlated with PC20 for methacholine, eosinophils and FEV1. Th2/Th17 cells, unlike Th2 cells, were resistant to dexamethasone-induced cell death. They expressed higher levels of MEK1, a molecule that induces glucocorticoid resistance. Based upon the dominance of BAL Th2 or Th2/Th17 cells, we identified three subgroups of asthma—Th2predominant, Th2/Th17predominant and Th2/Th17low. The Th2/Th17predominant subgroup manifested the most severe form of asthma whereas the Th2/Th17low subgroup had the mildest asthma. Conclusion Asthma is associated with a higher frequency of dual positive Th2/Th17 cells in BAL. The Th2/Th17predominant subgroup of asthmatic patients manifests glucocorticoid resistance in vitro. They also have the greatest airway obstruction and hyperreactivity as compared to Th2predominant and Th2/Th17low subgroups.
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Lambrecht, B. N., & Hammad, H. (2015) · Nature Immunology · doi:10.1038/ni.3049 · Cited by 1,673
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Stadhouders, R., Lubberts, E., & Hendriks, R. W. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.007 · Cited by 282
Emerging comorbidities in adult asthma: risks, clinical associations, and mechanisms
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Zhang, Z., Biagini Myers, J. M., Brandt, E. B., Ryan, P. H., Lindsey, M., Mintz-Cole, R. A., Reponen, T., Vesper, S. J., Forde, F., Ruff, B., et al. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.02.031 · Cited by 98
Sleep deprivation predisposes allergic mice to neutrophilic lung inflammation
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Metadata
- Authors
- Irvin, C., Zafar, I., Good, J., Rollins, D., Christianson, C., Gorska, M. M., Martin, R. J., & Alam, R.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 134
- Issue
- 5
- Pages
- 1175-1186.e7
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2048395646
- Cited by
- 317
- References
- 60
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- green
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- Irvin, C., Zafar, I., Good, J., Rollins, D., Christianson, C., Gorska, M. M., Martin, R. J., & Alam, R. (2014). Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2014.05.038
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