Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis
Abstract Background Investigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to cha...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-020-02410-w |
| _version_ | 1818407584244170752 |
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| author | Nils Rosshirt Richard Trauth Hadrian Platzer Elena Tripel Timo A. Nees Hanns-Martin Lorenz Theresa Tretter Babak Moradi |
| author_facet | Nils Rosshirt Richard Trauth Hadrian Platzer Elena Tripel Timo A. Nees Hanns-Martin Lorenz Theresa Tretter Babak Moradi |
| author_sort | Nils Rosshirt |
| collection | DOAJ |
| description | Abstract Background Investigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to characterize the involved cell populations, by investigating synovial fluid (SF) and synovial membrane (SM) of early OA patients for the presence and polarization status of CD4 T cells. Methods A quantitative analysis of CD4+ T cell infiltration in SF and SM compared to peripheral blood (PB) was performed in patients with early stages of OA. We further investigated intracellular staining (ICS), surface marker, and chemokine receptor expression profiles of CD4+ T cells in SF, SM, and PB, as well as cytokine expression in native SF and PB. Matched samples of SF, SM, and PB were harvested from 40 patients with early OA at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Samples were analyzed by flow cytometry for surface markers and cytokines, which are preferentially expressed by distinct T cell subsets (Th1, Th2, Th17, regulatory T cells). Furthermore, we analyzed native SF and PB supernatants using MACSPlex for multiple cytokine expression profiles. Results SF and SM showed a distinct infiltration of CD4+ T lymphocytes, with significantly increased expression of chemokine receptors CXCR3/CCR5, cytokine IFN-γ (preferentially expressed by Th1 cells), and CD161 (preferentially expressed by IL-17 producing Th17 cells) compared to PB. Furthermore, the percentage of CD4+ T cells polarized to Treg was significantly increased in SM compared to SF and PB. No significant differences were observed for CCR3 and CCR4 (preferentially expressed by Th2 cells), although IL-4 values were significantly higher in SM and SF compared to PB. Cytokine analysis showed comparable results between PB and SF, with only IL-6 being significantly increased in SF. Conclusions Early OA joints show already significant inflammation through CD4+ T cell infiltration, with predominant Th1 cell polarization. Inflammation seems to be driven by direct proinflammatory cell interaction. Cytokine signaling seems to be negligible at the site of inflammation in early OA, with only IL-6 being significantly increased in SF compared to PB. |
| first_indexed | 2024-12-14T09:30:09Z |
| format | Article |
| id | doaj.art-c40748faf6eb4c7c853a781f07e4d1e6 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-14T09:30:09Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-c40748faf6eb4c7c853a781f07e4d1e62022-12-21T23:08:05ZengBMCArthritis Research & Therapy1478-63622021-01-0123111210.1186/s13075-020-02410-wProinflammatory T cell polarization is already present in patients with early knee osteoarthritisNils Rosshirt0Richard Trauth1Hadrian Platzer2Elena Tripel3Timo A. Nees4Hanns-Martin Lorenz5Theresa Tretter6Babak Moradi7Clinic for Orthopedic and Trauma Surgery, University Hospital HeidelbergClinic for Orthopedic and Trauma Surgery, University Hospital HeidelbergClinic for Orthopedic and Trauma Surgery, University Hospital HeidelbergClinic for Orthopedic and Trauma Surgery, University Hospital HeidelbergClinic for Orthopedic and Trauma Surgery, University Hospital HeidelbergDepartment of Internal Medicine V, Division of Rheumatology, University Hospital HeidelbergDepartment of Internal Medicine V, Division of Rheumatology, University Hospital HeidelbergClinic of Orthopedic and Trauma Surgery, University of KielAbstract Background Investigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to characterize the involved cell populations, by investigating synovial fluid (SF) and synovial membrane (SM) of early OA patients for the presence and polarization status of CD4 T cells. Methods A quantitative analysis of CD4+ T cell infiltration in SF and SM compared to peripheral blood (PB) was performed in patients with early stages of OA. We further investigated intracellular staining (ICS), surface marker, and chemokine receptor expression profiles of CD4+ T cells in SF, SM, and PB, as well as cytokine expression in native SF and PB. Matched samples of SF, SM, and PB were harvested from 40 patients with early OA at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Samples were analyzed by flow cytometry for surface markers and cytokines, which are preferentially expressed by distinct T cell subsets (Th1, Th2, Th17, regulatory T cells). Furthermore, we analyzed native SF and PB supernatants using MACSPlex for multiple cytokine expression profiles. Results SF and SM showed a distinct infiltration of CD4+ T lymphocytes, with significantly increased expression of chemokine receptors CXCR3/CCR5, cytokine IFN-γ (preferentially expressed by Th1 cells), and CD161 (preferentially expressed by IL-17 producing Th17 cells) compared to PB. Furthermore, the percentage of CD4+ T cells polarized to Treg was significantly increased in SM compared to SF and PB. No significant differences were observed for CCR3 and CCR4 (preferentially expressed by Th2 cells), although IL-4 values were significantly higher in SM and SF compared to PB. Cytokine analysis showed comparable results between PB and SF, with only IL-6 being significantly increased in SF. Conclusions Early OA joints show already significant inflammation through CD4+ T cell infiltration, with predominant Th1 cell polarization. Inflammation seems to be driven by direct proinflammatory cell interaction. Cytokine signaling seems to be negligible at the site of inflammation in early OA, with only IL-6 being significantly increased in SF compared to PB.https://doi.org/10.1186/s13075-020-02410-wEarly OAT cell polarizationT helper cellsInflammatory T cellsSynovial membraneSynovial fluid |
| spellingShingle | Nils Rosshirt Richard Trauth Hadrian Platzer Elena Tripel Timo A. Nees Hanns-Martin Lorenz Theresa Tretter Babak Moradi Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis Arthritis Research & Therapy Early OA T cell polarization T helper cells Inflammatory T cells Synovial membrane Synovial fluid |
| title | Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis |
| title_full | Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis |
| title_fullStr | Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis |
| title_full_unstemmed | Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis |
| title_short | Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis |
| title_sort | proinflammatory t cell polarization is already present in patients with early knee osteoarthritis |
| topic | Early OA T cell polarization T helper cells Inflammatory T cells Synovial membrane Synovial fluid |
| url | https://doi.org/10.1186/s13075-020-02410-w |
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