Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation
The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, and quantitative way to pre...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Rockefeller University Press
2023
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| _version_ | 1811139409500700672 |
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| author | Zec, K Schonfeldova, B Ai, Z Van Grinsven, E Pirgova, G Eames, HL Berthold, DL Attar, M Compeer, EB Arnon, T Udalova, IA |
| author_facet | Zec, K Schonfeldova, B Ai, Z Van Grinsven, E Pirgova, G Eames, HL Berthold, DL Attar, M Compeer, EB Arnon, T Udalova, IA |
| author_sort | Zec, K |
| collection | OXFORD |
| description | The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, and quantitative way to present evidence that synovial inflammation begins with the activation of lining macrophages. We show that lining, but not sublining macrophages phagocytose immune complexes containing the model antigen. Using the antigen-induced arthritis (AIA) model, we demonstrate that on recognition of antigen-antibody complexes, lining macrophages undergo significant activation, which is dependent on interferon regulatory factor 5 (IRF5), and produce chemokines, most notably CXCL1. Consequently, at the onset of inflammation, neutrophils are preferentially recruited in the vicinity of antigen-laden macrophages in the synovial lining niche. As inflammation progresses, neutrophils disperse across the whole synovium and form swarms in synovial sublining during resolution. Our study alters the paradigm of lining macrophages as immunosuppressive cells to important instigators of synovial inflammation. |
| first_indexed | 2024-09-25T04:05:38Z |
| format | Journal article |
| id | oxford-uuid:aeea749c-1f8d-43ff-9b40-e20b52ebbed1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:05:38Z |
| publishDate | 2023 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:aeea749c-1f8d-43ff-9b40-e20b52ebbed12024-05-21T14:51:34ZMacrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aeea749c-1f8d-43ff-9b40-e20b52ebbed1EnglishSymplectic ElementsRockefeller University Press2023Zec, KSchonfeldova, BAi, ZVan Grinsven, EPirgova, GEames, HLBerthold, DLAttar, MCompeer, EBArnon, TUdalova, IAThe first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, and quantitative way to present evidence that synovial inflammation begins with the activation of lining macrophages. We show that lining, but not sublining macrophages phagocytose immune complexes containing the model antigen. Using the antigen-induced arthritis (AIA) model, we demonstrate that on recognition of antigen-antibody complexes, lining macrophages undergo significant activation, which is dependent on interferon regulatory factor 5 (IRF5), and produce chemokines, most notably CXCL1. Consequently, at the onset of inflammation, neutrophils are preferentially recruited in the vicinity of antigen-laden macrophages in the synovial lining niche. As inflammation progresses, neutrophils disperse across the whole synovium and form swarms in synovial sublining during resolution. Our study alters the paradigm of lining macrophages as immunosuppressive cells to important instigators of synovial inflammation. |
| spellingShingle | Zec, K Schonfeldova, B Ai, Z Van Grinsven, E Pirgova, G Eames, HL Berthold, DL Attar, M Compeer, EB Arnon, T Udalova, IA Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title_full | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title_fullStr | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title_full_unstemmed | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title_short | Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
| title_sort | macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation |
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