Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica
BackgroundGiant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in t...
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1201575/full |
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| author | Rosanne D. Reitsema Rosanne D. Reitsema Bernd-Cornèl Hesselink Wayel H. Abdulahad Wayel H. Abdulahad Kornelis S. M. van der Geest Elisabeth Brouwer Peter Heeringa Yannick van Sleen |
| author_facet | Rosanne D. Reitsema Rosanne D. Reitsema Bernd-Cornèl Hesselink Wayel H. Abdulahad Wayel H. Abdulahad Kornelis S. M. van der Geest Elisabeth Brouwer Peter Heeringa Yannick van Sleen |
| author_sort | Rosanne D. Reitsema |
| collection | DOAJ |
| description | BackgroundGiant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.MethodsAPCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c).Resultst-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs.ConclusionCirculating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated. |
| first_indexed | 2024-03-12T18:00:42Z |
| format | Article |
| id | doaj.art-c1fdee70017543ecbe09a34c36c96e07 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T18:00:42Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c1fdee70017543ecbe09a34c36c96e072023-08-02T12:46:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12015751201575Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumaticaRosanne D. Reitsema0Rosanne D. Reitsema1Bernd-Cornèl Hesselink2Wayel H. Abdulahad3Wayel H. Abdulahad4Kornelis S. M. van der Geest5Elisabeth Brouwer6Peter Heeringa7Yannick van Sleen8Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsSchool of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, SwedenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsBackgroundGiant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.MethodsAPCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c).Resultst-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs.ConclusionCirculating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1201575/fullgiant cell arteritispolymyalgia rheumaticamonocytesdendritic cellsvasculitis |
| spellingShingle | Rosanne D. Reitsema Rosanne D. Reitsema Bernd-Cornèl Hesselink Wayel H. Abdulahad Wayel H. Abdulahad Kornelis S. M. van der Geest Elisabeth Brouwer Peter Heeringa Yannick van Sleen Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica Frontiers in Immunology giant cell arteritis polymyalgia rheumatica monocytes dendritic cells vasculitis |
| title | Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| title_full | Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| title_fullStr | Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| title_full_unstemmed | Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| title_short | Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| title_sort | aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica |
| topic | giant cell arteritis polymyalgia rheumatica monocytes dendritic cells vasculitis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1201575/full |
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