Th17-Zellen während der Ontogenese und bei der chronisch obstruktiven Lungenerkrankung

Th17-Zellen sind CD3+CD4+CD161+CCR6+-Lymphozyten, die nach Stimulation IL-17A, IL-17F und IL-22 produzieren. Dieser T-Zell-Subtyp bildet neben Th1- und Th2-Zellen eine wichtige Säule der T-Zell-vermittelten Pathogen-Elimination und spielt vermutlich auch bei der Pathogenese von Autoimmunerkrankungen...

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Bibliographic Details
Main Author: Coccejus, Verena
Contributors: Maier, R. (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2020
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Th17-cells are CD3+CD4+CD161+CCR6+-lymphocytes which are able to produce IL-17A, IL-17F and IL-22 after stimulation. In addition to Th1- and Th2-cells, this T-cell subtype is an important pillar of T-cell-mediated pathogen elimination and is believed to play an important role in the pathogenesis of autoimmune diseases and allergies. This T-cell subtype appears to be involved in the defense against bacterial and fungal infections on epithelial surfaces, especially in premature infants and full-term newborns. Th17-cells are also involved in the pathogenesis of chronic respiratory disease. Especially Chronic obstructive pulmonary disease (COPD) seems to be associated with persistent inflammation and bronchial obstruction caused by remodeling due to a mismatch of pro-inflammatory Th17-cells and protective Treg-cells. The aim of this study was to investigate whether Th17-cells are already detectable in neonates and whether their proportion increases until adulthood. In addition, stimulation for IL-17 production should be observed. In addition, the question should be clarified whether COPD patients have a higher proportion of Th17-cells and whether there is a connection to the measure of airway obstruction. To clarify the above question, native Th17-cells with the surface characteristics CD3+ CD4+CD161+CCR6+ were determined by flow cytometry. A further flow cytometric determination was performed on cells after short-term stimulation with ionomycin and the characteristics CD3+CD4+IL-17+. In addition, qPCR was used on cells before and after short-term stimulation to study the expression of RORɣt and IL-17. Using flow cytometry, this work demonstrated that Th17-cells were already present in the umbilical cord blood of 17 neonates and could be stimulated to induce IL-17 secretion by short-term stimulation with ionomycin. This stimulability of newborn Th17-cells increased with gestational age (p < 0,05). In addition, the number of circulating Th17 cells in the peripheral blood increased from neonatal age to infancy (21 healthy subjects) to adulthood (13 healthy subjects) (p < 0,01). At the gene level, as in previous studies, it could be shown that RORɣt expression declined with increasing maturity of newborns, suggesting that predilection for the Th17 cell response is associated with increasing immaturity. It can’t be excluded, that the increased susceptibility to infections of premature infants is a result of the low Th17-cell stimulability. It is thought that Th17-cells play a role in the pathogenesis of COPD. In this study, the proportion of Th17-cell did not differ significantly between 13 healthy volunteers and 13 patients with COPD. In contrast, the Th17-cell fraction of Th cells correlated negatively with the one second capacity (p < 0,05). Therefore, Th17-cells may be useful as biomarkers for COPD.