CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired
There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid art...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/3/549 |
| _version_ | 1827880054381608960 |
|---|---|
| author | Magdalena Massalska Anna Radzikowska Ewa Kuca-Warnawin Magdalena Plebanczyk Monika Prochorec-Sobieszek Urszula Skalska Weronika Kurowska Pawel Maldyk Ewa Kontny Hans-Jürgen Gober Wlodzimierz Maslinski |
| author_facet | Magdalena Massalska Anna Radzikowska Ewa Kuca-Warnawin Magdalena Plebanczyk Monika Prochorec-Sobieszek Urszula Skalska Weronika Kurowska Pawel Maldyk Ewa Kontny Hans-Jürgen Gober Wlodzimierz Maslinski |
| author_sort | Magdalena Massalska |
| collection | DOAJ |
| description | There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [<sup>3</sup>H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4<sup>+</sup>FOXP3<sup>+</sup> T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7α receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4<sup>+</sup>FOXP3<sup>+</sup> cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4<sup>+</sup>FOXP3<sup>+</sup> T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM. |
| first_indexed | 2024-03-12T18:15:29Z |
| format | Article |
| id | doaj.art-abe3a37486d44ccfb3bdf2b5faff881d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T18:15:29Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-abe3a37486d44ccfb3bdf2b5faff881d2023-08-02T09:09:45ZengMDPI AGCells2073-44092020-02-019354910.3390/cells9030549cells9030549CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially ImpairedMagdalena Massalska0Anna Radzikowska1Ewa Kuca-Warnawin2Magdalena Plebanczyk3Monika Prochorec-Sobieszek4Urszula Skalska5Weronika Kurowska6Pawel Maldyk7Ewa Kontny8Hans-Jürgen Gober9Wlodzimierz Maslinski10Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Rheumoorthopaedic Surgery, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandDepartment of Pharmacy, Kepler University Hospital, 4020 Linz, AustriaDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, 02-637 Warsaw, PolandThere is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [<sup>3</sup>H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4<sup>+</sup>FOXP3<sup>+</sup> T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7α receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4<sup>+</sup>FOXP3<sup>+</sup> cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4<sup>+</sup>FOXP3<sup>+</sup> T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM.https://www.mdpi.com/2073-4409/9/3/549bone marrowcd4<sup>+</sup>foxp3<sup>+</sup>treg cellsrheumatoid arthritisimmunosuppression |
| spellingShingle | Magdalena Massalska Anna Radzikowska Ewa Kuca-Warnawin Magdalena Plebanczyk Monika Prochorec-Sobieszek Urszula Skalska Weronika Kurowska Pawel Maldyk Ewa Kontny Hans-Jürgen Gober Wlodzimierz Maslinski CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired Cells bone marrow cd4<sup>+</sup>foxp3<sup>+</sup> treg cells rheumatoid arthritis immunosuppression |
| title | CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired |
| title_full | CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired |
| title_fullStr | CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired |
| title_full_unstemmed | CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired |
| title_short | CD4<sup>+</sup>FOXP3<sup>+</sup> T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired |
| title_sort | cd4 sup sup foxp3 sup sup t cells in rheumatoid arthritis bone marrow are partially impaired |
| topic | bone marrow cd4<sup>+</sup>foxp3<sup>+</sup> treg cells rheumatoid arthritis immunosuppression |
| url | https://www.mdpi.com/2073-4409/9/3/549 |
| work_keys_str_mv | AT magdalenamassalska cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT annaradzikowska cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT ewakucawarnawin cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT magdalenaplebanczyk cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT monikaprochorecsobieszek cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT urszulaskalska cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT weronikakurowska cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT pawelmaldyk cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT ewakontny cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT hansjurgengober cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired AT wlodzimierzmaslinski cd4supsupfoxp3supsuptcellsinrheumatoidarthritisbonemarrowarepartiallyimpaired |