title: Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation.
abstract: Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M.
authors.affiliation: Department of Internal Medicine I, Laboratory for Tumorgenetics, University Hospital Cologne, Cologne, Germany. gunter.rappl@uni-koeln.de
authors.forename: Gunter
authors.initials: G
authors.lastname: Rappl
authors.forename: Stefan
authors.initials: S
authors.lastname: Pabst
authors.forename: Dagmar
authors.initials: D
authors.lastname: Riemann
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schütte
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Hombach
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006099:Granuloma / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult