Artikel
Expression of inhibitory receptor PIR-B on peripheral T cells in arthritis mouse model
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Autoren
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Kathrin Rothe
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Dagmar Quandt
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
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Gabriele Köhler
- Institute of Pathology, Fulda
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Ulf Wagner
- Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Rheumatologie, Leipzig
| Veröffentlicht: | 8. Oktober 2019 |
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Gliederung
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Background: T cells in rheumatoid arthritis are dysregulated with a pro-inflammatory cytokine profile. We previously identified a subset of effector-memory CD8+ and CD4+ T cell which are characterized by the expression of inhibitory receptor LIR-1 and an increased cytolytic potential. To elucidate the in vivo role of LIR-1+ T cells, we investigated the expression of its orthologue PIR-B in SKG and collagen-induced arthritis (CIA) mouse model.
Methods: Surface expression of PIR-B on CD8+ and CD4+ T cells from spleen, lymph nodes and peripheral blood was analyzed using flow cytometry and RT-PCR. For functional studies, isolated T cells were stimulated via PMA/ionomycin and production of IL-17 and IFN-γ was analyzed immediately. Arthritis score was analyzed after arthritis induction by evaluation of paw swelling. In a blinded fashion, histological analysis of synovial sections was performed after H&E staining by evaluation of inflammation and cell infiltration.
Results: SKG mice show increased frequencies of splenic PIR-B+ T cells in comparison to age-matched wildtype background mice. Additionally, arthritis induction supports expansion of PIR-B+ T cells. Stimulation with PMA/ionomycin revealed that PIR-B+ T cells are mainly pro-inflammatory by a large production of IFN-γ and contain a subset of IL-17 producer. In contrast to cytokine production, frequencies of PIR-B+ T cells were negatively associated with arthritis or histological score.
Conclusion: We are the first, who showed expression of inhibitory receptor PIR-B on peripheral T cells in SKG and CIA mouse model. PIR-B+ T cells seem to take part in arthritis pathogenesis, since the number negatively correlates with arthritis disease severity.
