GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis
Background and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patient...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.613975/full |
| _version_ | 1818609803184832512 |
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| author | Sara Fuentelsaz-Romero Andrea Cuervo Lizbeth Estrada-Capetillo Raquel Celis Raquel García-Campos Julio Ramírez Sergi Sastre Rafael Samaniego Amaya Puig-Kröger Juan D. Cañete |
| author_facet | Sara Fuentelsaz-Romero Andrea Cuervo Lizbeth Estrada-Capetillo Raquel Celis Raquel García-Campos Julio Ramírez Sergi Sastre Rafael Samaniego Amaya Puig-Kröger Juan D. Cañete |
| author_sort | Sara Fuentelsaz-Romero |
| collection | DOAJ |
| description | Background and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.MethodsSynovial tissue (ST) from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12, and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.ResultsSynovial stromal cells (FAP+ CD90+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα, and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypes showed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA.ConclusionsGM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA. |
| first_indexed | 2024-12-16T15:04:20Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T15:04:20Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-f963dba0a75f43d589c8b4d1e93ba7dd2022-12-21T22:27:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.613975613975GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic ArthritisSara Fuentelsaz-Romero0Andrea Cuervo1Lizbeth Estrada-Capetillo2Raquel Celis3Raquel García-Campos4Julio Ramírez5Sergi Sastre6Rafael Samaniego7Amaya Puig-Kröger8Juan D. Cañete9Unidad de Inmuno-Metabolismo e Inflamación, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, SpainUnidad de Artritis, Servicio de Reumatología, Hospital Clínic and IDIBAPS, Barcelona, SpainUnidad de Inmuno-Metabolismo e Inflamación, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, SpainUnidad de Artritis, Servicio de Reumatología, Hospital Clínic and IDIBAPS, Barcelona, SpainUnidad de Inmuno-Metabolismo e Inflamación, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, SpainUnidad de Artritis, Servicio de Reumatología, Hospital Clínic and IDIBAPS, Barcelona, SpainSección de Artroscopia, Servicio de Cirugía Ortopédica y Traumatología, Hospital Clínic, Barcelona, SpainUnidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, SpainUnidad de Inmuno-Metabolismo e Inflamación, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, SpainUnidad de Artritis, Servicio de Reumatología, Hospital Clínic and IDIBAPS, Barcelona, SpainBackground and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.MethodsSynovial tissue (ST) from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12, and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.ResultsSynovial stromal cells (FAP+ CD90+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα, and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypes showed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA.ConclusionsGM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.https://www.frontiersin.org/articles/10.3389/fimmu.2020.613975/fullGM-CSFmacrophagessynovial tissueundifferentiated arthritispsoriatic arthritisrheumatoid arthritis |
| spellingShingle | Sara Fuentelsaz-Romero Andrea Cuervo Lizbeth Estrada-Capetillo Raquel Celis Raquel García-Campos Julio Ramírez Sergi Sastre Rafael Samaniego Amaya Puig-Kröger Juan D. Cañete GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis Frontiers in Immunology GM-CSF macrophages synovial tissue undifferentiated arthritis psoriatic arthritis rheumatoid arthritis |
| title | GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis |
| title_full | GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis |
| title_fullStr | GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis |
| title_full_unstemmed | GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis |
| title_short | GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis |
| title_sort | gm csf expression and macrophage polarization in joints of undifferentiated arthritis patients evolving to rheumatoid arthritis or psoriatic arthritis |
| topic | GM-CSF macrophages synovial tissue undifferentiated arthritis psoriatic arthritis rheumatoid arthritis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.613975/full |
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