title: Regulation of IL-17 in chronic inflammation in the human lung.
abstract: The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4(+)CD25(+)) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4(+)CD25(+) T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4(+)CD25(+) T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4(+)CD25(+) T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.
authors.affiliation: Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Pridgeon
authors.forename: Laurence
authors.initials: L
authors.lastname: Bugeon
authors.forename: Louise
authors.initials: L
authors.lastname: Donnelly
authors.forename: Ursula
authors.initials: U
authors.lastname: Straschil
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Tudhope
authors.forename: Peter
authors.initials: P
authors.lastname: Fenwick
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Dallman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma