Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Milger, K; Yu, Y; Brudy, E; Irmler, M; Skapenko, A; Mayinger, M; Lehmann, M; Beckers, J; Reichenberger, F; Behr, J; Eickelberg, O; Königshoff, M; Krauss-Etschmann, S.
Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development.
Thorax. 2017; 72(11): 1007-1020.
Doi: 10.1136/thoraxjnl-2016-208423
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Milger-Kneidinger Katrin
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- Abstract:
- BACKGROUND: Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2+CD4+ T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2+ cell populations might either increase or decrease disease pathogenesis depending on their subtype. OBJECTIVE: To investigate the role of CCR2+CD4+ T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. METHODS: Pulmonary CCR2+CD4+ T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. RESULTS: Frequencies of CCR2+CD4+ T cells were increased in experimental fibrosis-specifically the CD62L-CD44+ effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2+CD4+ T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2+CD4+ T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3+ CD25+ cells within bronchoalveolar lavage fluid CCR2+CD4+ T cells as compared with CCR2-CD4+ T cells. CONCLUSION: Pulmonary CCR2+CD4+ T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Biomarkers - metabolism
- Bronchoalveolar Lavage Fluid - immunology
- CD4-Positive T-Lymphocytes - immunology
- Disease Models, Animal - administration & dosage
- Female - administration & dosage
- Humans - administration & dosage
- Lung Diseases, Interstitial - diagnosis, immunology
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Phenotype - administration & dosage
- Predictive Value of Tests - administration & dosage
- Receptors, CCR2 - immunology
- Sensitivity and Specificity - administration & dosage
- Severity of Illness Index - administration & dosage
- T-Lymphocytes, Regulatory - immunology