Article
Evidence of platelet – T-cell cross-talk in granulomatosis with polyangiitis
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Authors
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Anja Kerstein
- Klinik für Rheumatologie und Klinische Immunologie, Universität zu Lübeck, Lübeck
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Sebastian Klapa
- Institut für experimentelle Medizin, Sektion Maritime Medizin, Christian-Albrechts-Universität zu Kiel und Klinik für Rheumatologie und Klinische Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Kronshagen
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Silke Pitann
- Klinik für Rheumatologie und Klinische Immunologie, Universität zu Lübeck, Lübeck
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Kerstin Mosenthin
- Klinik für Rheumatologie und Klinische Immunologie, Universität zu Lübeck, Lübeck
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Antje Müller
- Klinik für Rheumatologie und Klinische Immunologie, Universität zu Lübeck, Lübeck
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Gabriela Riemekasten
- Universität zu Lübeck, Klinik für Rheumatologie und Klinische Immunologie, Lübeck
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Peter Lamprecht
- Klinik für Rheumatologie und Klinische Immunologie, Universität zu Lübeck, Lübeck
| Published: | February 5, 2019 |
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Outline
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Background: Cross-talk of platelets and leukocytes is involved in immune-mediated pathologies. In granulomatosis with polyangiitis (GPA), a systemic autoimmune vasculitis, increased platelet counts and platelet markers correlate with disease activity. Here we provide evidence that platelets are directly involved in T-cell-mediated pathophysiology in GPA.
Methods: We analyzed the transcriptomic profile of sorted CD4+ and CD8+ single-positive and CD4+CD8+ double positive (DP) T-cells in GPA and healthy controls (HC, each n=3) using an Affymetrix Human Genome 2.0 microarray. Differently expressed genes (DEG) were further categorized by GO functional enrichment analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) PATHWAY database. Protein-protein interaction networks were visualized by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Adhering platelets on T-cells were detected by measuring the surface expression of platelet glycoprotein IIb (CD41) on gated T-cell populations from GPA (n=9) and HC (n=6) with FACS.
Results: By comparing the transcriptomic profile of sorted T-cell populations from GPA to HC, we found upregulated genes enriched in pathways related to leukocyte transendothelial migration, complement and coagulation cascades, platelet activation and cell adhesion molecules in GPA. Functional protein-protein interaction networks in pathways associated with platelet activation, signaling, aggregation and cell surface interaction at the vascular wall were identified and visualized by STRING. CD41 expression was increased on CD4+CD8+ DP T-cells suggestive of platelet-coated T-cell populations in GPA.
Conclusion: To summarize, on transcriptomic as well as phenotypic level we provide evidence for a direct interaction of platelets and T-cells resulting in the activation of pathways involving adhesion and migration through the vascular epithelium. Given the potential impact of T-cells on GPA pathology such as vascular injury and tissue damage, this finding represents a field of research and implies new targets for future therapies.
