Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high...
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/3161750 |
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| author | Lisa Deloch Jana Fuchs Michael Rückert Rainer Fietkau Benjamin Frey Udo S. Gaipl |
| author_facet | Lisa Deloch Jana Fuchs Michael Rückert Rainer Fietkau Benjamin Frey Udo S. Gaipl |
| author_sort | Lisa Deloch |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of hTNF-α tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions. |
| format | Article |
| id | doaj-art-7d6ae4880dcd4e6fa5ecd8d9ffbb95d8 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-7d6ae4880dcd4e6fa5ecd8d9ffbb95d82025-02-03T06:48:37ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/31617503161750Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation DoseLisa Deloch0Jana Fuchs1Michael Rückert2Rainer Fietkau3Benjamin Frey4Udo S. Gaipl5Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen 91054, GermanyRheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of hTNF-α tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions.http://dx.doi.org/10.1155/2019/3161750 |
| spellingShingle | Lisa Deloch Jana Fuchs Michael Rückert Rainer Fietkau Benjamin Frey Udo S. Gaipl Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose Journal of Immunology Research |
| title | Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose |
| title_full | Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose |
| title_fullStr | Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose |
| title_full_unstemmed | Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose |
| title_short | Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose |
| title_sort | low dose irradiation differentially impacts macrophage phenotype in dependence of fibroblast like synoviocytes and radiation dose |
| url | http://dx.doi.org/10.1155/2019/3161750 |
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