Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells
Abstract The JAK/STAT pathway plays a crucial role in the pathogenesis of rheumatoid arthritis (RA) and JAK inhibitors have emerged as a new group of effective drugs for RA treatment. Recently, high STAT3 levels have been associated with the upregulation of the scaffold protein NEDD9, which is a reg...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.15829 |
| _version_ | 1797397420890390528 |
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| author | Viktoria Golumba‐Nagy Shuaifeng Yan Eva Steinbach‐Knödgen Jan Thiele Ruth L. Esser Thomas H. Haak Anastasia Nikiforov Anja Meyer Tamina Seeger‐Nukpezah David M. Kofler |
| author_facet | Viktoria Golumba‐Nagy Shuaifeng Yan Eva Steinbach‐Knödgen Jan Thiele Ruth L. Esser Thomas H. Haak Anastasia Nikiforov Anja Meyer Tamina Seeger‐Nukpezah David M. Kofler |
| author_sort | Viktoria Golumba‐Nagy |
| collection | DOAJ |
| description | Abstract The JAK/STAT pathway plays a crucial role in the pathogenesis of rheumatoid arthritis (RA) and JAK inhibitors have emerged as a new group of effective drugs for RA treatment. Recently, high STAT3 levels have been associated with the upregulation of the scaffold protein NEDD9, which is a regulator of T‐cell trafficking and promotes collagen‐induced arthritis (CIA). In this study, we aimed to reveal how treatment with JAK inhibitors affects NEDD9 in CD4+ T cells from RA patients. We analyzed NEDD9 expression in CD4+ T cells from 50 patients treated with either baricitinib, tofacitinib, or upadacitinib and performed cell migration assays to assess the potential influence of JAK inhibitor treatment on CD4+ T‐cell migration. We observed that treatment with baricitinib and upadacitinib is associated with reduced NEDD9 expression in CD4+ T cells. In contrast, NEDD9 levels were not altered during treatment with tofacitinib. Moreover, treatment with baricitinib was associated with a significantly reduced migratory capacity of effector CD4+ T cells but not with impaired migration of Treg cells. This study reveals previously unknown associations between JAK inhibitor treatment and NEDD9 expression and indicates that JAK inhibitors could reduce effector T‐cell migration. |
| first_indexed | 2024-03-09T01:10:44Z |
| format | Article |
| id | doaj.art-81438bdbe9c5496dade440d63be182ff |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-09T01:10:44Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-81438bdbe9c5496dade440d63be182ff2023-12-11T07:16:19ZengWileyPhysiological Reports2051-817X2023-10-011119n/an/a10.14814/phy2.15829Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cellsViktoria Golumba‐Nagy0Shuaifeng Yan1Eva Steinbach‐Knödgen2Jan Thiele3Ruth L. Esser4Thomas H. Haak5Anastasia Nikiforov6Anja Meyer7Tamina Seeger‐Nukpezah8David M. Kofler9Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyLaboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne Cologne GermanyAbstract The JAK/STAT pathway plays a crucial role in the pathogenesis of rheumatoid arthritis (RA) and JAK inhibitors have emerged as a new group of effective drugs for RA treatment. Recently, high STAT3 levels have been associated with the upregulation of the scaffold protein NEDD9, which is a regulator of T‐cell trafficking and promotes collagen‐induced arthritis (CIA). In this study, we aimed to reveal how treatment with JAK inhibitors affects NEDD9 in CD4+ T cells from RA patients. We analyzed NEDD9 expression in CD4+ T cells from 50 patients treated with either baricitinib, tofacitinib, or upadacitinib and performed cell migration assays to assess the potential influence of JAK inhibitor treatment on CD4+ T‐cell migration. We observed that treatment with baricitinib and upadacitinib is associated with reduced NEDD9 expression in CD4+ T cells. In contrast, NEDD9 levels were not altered during treatment with tofacitinib. Moreover, treatment with baricitinib was associated with a significantly reduced migratory capacity of effector CD4+ T cells but not with impaired migration of Treg cells. This study reveals previously unknown associations between JAK inhibitor treatment and NEDD9 expression and indicates that JAK inhibitors could reduce effector T‐cell migration.https://doi.org/10.14814/phy2.15829baricitinibCD4+ T cellsNEDD9rheumatoid arthritistofacitinibupadacitinib |
| spellingShingle | Viktoria Golumba‐Nagy Shuaifeng Yan Eva Steinbach‐Knödgen Jan Thiele Ruth L. Esser Thomas H. Haak Anastasia Nikiforov Anja Meyer Tamina Seeger‐Nukpezah David M. Kofler Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells Physiological Reports baricitinib CD4+ T cells NEDD9 rheumatoid arthritis tofacitinib upadacitinib |
| title | Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells |
| title_full | Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells |
| title_fullStr | Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells |
| title_full_unstemmed | Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells |
| title_short | Treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein NEDD9 levels in CD4+ T cells |
| title_sort | treatment of rheumatoid arthritis with baricitinib or upadacitinib is associated with reduced scaffold protein nedd9 levels in cd4 t cells |
| topic | baricitinib CD4+ T cells NEDD9 rheumatoid arthritis tofacitinib upadacitinib |
| url | https://doi.org/10.14814/phy2.15829 |
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