Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica

Frontiers in Immunology

Immunology

Peter Heeringa¹  Bernd-Cornèl Hesselink²  Kornelis S. M. van der Geest²  Yannick van Sleen²  Elisabeth Brouwer²  Wayel H. Abdulahad³  Rosanne D. Reitsema⁴ 

[1] Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands;School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden;

关键词: giant cell arteritis;    polymyalgia rheumatica;    monocytes;    dendritic cells;    vasculitis;   

DOI  :  10.3389/fimmu.2023.1201575

 received in 2023-04-06, accepted in 2023-07-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Reitsema, Hesselink, Abdulahad, van der Geest, Brouwer, Heeringa and van Sleen