Biomarkers for comorbidities modulate the activity of T-cells in COPD
- In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total \(\it n\) = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP; chemokine (C-C motif) ligand 18, CCL18; C-X3-C motif chemokine ligand 1, CX3CL1; interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22; epidermal growth factor, EGF; IL-17; periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-\(\gamma\) (IFN\(\gamma\)), tumor necrosis factor-\(\alpha\) (TNF\(\alpha\)), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFN\(\gamma\) and TNF\(\alpha\) without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma- and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.
Author: | Kaschin Jamal JameelGND, Willem-Jakob GallertGND, Sarah Derya YanikGND, Susanne PanekGND, Juliane KronsbeinGND, David JungckGND, Andrea KochGND, Jürgen KnoblochORCiDGND |
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URN: | urn:nbn:de:hbz:294-87696 |
DOI: | https://doi.org/10.3390/ijms22137187 |
Parent Title (English): | International journal of molecular sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/24 |
Date of first Publication: | 2021/07/02 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds COPD; T-cells; comorbidities |
Volume: | 22 |
Issue: | 13 |
First Page: | 7187-1 |
Last Page: | 7187-16 |
Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Medizinische Klinik III, Pneumologie, Allergologie, Schlaf- und Beatmungsmedizin |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (German): | Creative Commons - CC BY 4.0 - Namensnennung 4.0 International |