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Expanded lung T-bet...
Expanded lung T-bet+RORγT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype
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- Kaiser, Y (author)
- Karolinska Institutet
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- Lepzien, R (author)
- Karolinska Institutet
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Kullberg, S (author)
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- Eklund, A (author)
- Karolinska Institutet
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- Smed-Sorensen, A (author)
- Karolinska Institutet
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- Grunewald, J (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-05-26
- 2016
- English.
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 48:2, s. 484-494
- Related links:
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https://erj.ersjourn...
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https://doi.org/10.1...
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Abstract
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- Disease phenotypes of pulmonary sarcoidosis are distinguished by clinical rather than immunological criteria. We aimed to characterise patterns of CD4+ T-cell lineage plasticity underlying the differences in clinical presentation and disease course between the acute form, Löfgren's syndrome, and the heterogeneous, potentially progressive “non-Löfgren” form.33 pulmonary sarcoidosis patients and nine controls underwent bronchoscopy with bronchoalveolar lavage. CD4+ T-cell transcription factor, chemokine receptor and T-cell receptor expression, proliferation and cytokine production were assessed in the lavage fluid and peripheral blood using flow cytometry and multicolour FluoroSpot.CD4+ T-cells simultaneously expressing the T-helper cell (Th)1 and Th17 transcriptional regulators T-bet and RORγT (T-bet+RORγT+) were identified in the lavage, but not blood, of all subjects, and to a significantly higher degree in Löfgren's patients. T-bet+RORγT+ cells proliferated actively, produced interferon (IFN)γ and interleukin (IL)-17A, co-expressed the chemokine receptors CXCR3 and CCR6, and correlated with nonchronic disease. T-cell receptor-restricted Vα2.3+Vβ22+ T-cells strongly co-expressed T-bet/RORγT and CXCR3/CCR6. Cytokine production was more heterogeneous in Löfgren's patients, with significantly higher IL-17A, IL-10, IL-22 and IL-2, but lower IFNγ.Here we demonstrate the presence of lung T-bet+RORγT+CXCR3+CCR6+ CD4+ T-cells and Th17-associated cytokines especially in sarcoidosis patients with a favourable prognosis, suggesting a Th1/Th17-permissive environment in the lung with implications for disease resolution.
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- ref (subject category)
- art (subject category)
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