title: Expanded lung T-bet+RORγT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype.
abstract: 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.
authors.affiliation: Respiratory Medicine Unit, Dept of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden ylva.kaiser@ki.se.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Kaiser
authors.affiliation: Immunology and Allergy Unit, Dept of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Rico
authors.initials: R
authors.lastname: Lepzien
authors.affiliation: Respiratory Medicine Unit, Dept of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Kullberg
authors.affiliation: Respiratory Medicine Unit, Dept of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.affiliation: Immunology and Allergy Unit, Dept of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.affiliation: Respiratory Medicine Unit, Dept of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
mesh_terms: D000328:Adult; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016022:Case-Control Studies; D019070:Cell Lineage; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012507:Sarcoidosis / Q000503:physiopathology*; D017565:Sarcoidosis, Pulmonary / Q000503:physiopathology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3