cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non-Hodgkin orbital lymphoma and idiopathic orbital inflammation
Laban, Kamil G.; Rijken, Rianne; Hiddingh, Sanne; Mertens, Jorre S.; van der Veen, Rob L.P.; Eenhorst, Christine A.E.; Pandit, Aridaman; Radstake, Timothy R.D.J.; de Boer, Joke H.; Kalmann, Rachel; Kuiper, Jonas J.W.
(2020) European Journal of Immunology, volume 50, issue 4, pp. 548 - 557
(Article)
Abstract
Non-Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology. To investigate the immune cell composition of these diseases, we performed standardized 29 parameter flow cytometry phenotyping in peripheral blood mononuclear cells of 18 NHOL patients, 21 IOI patients, and 41 unaffected controls.
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Automatic gating by FlowSOM revealed decreased abundance of meta-clusters containing dendritic cells in patients, which we confirmed by manual gating. A decreased percentage of (HLA-DR+CD303+CD123+) plasmacytoid dendritic cells (pDC) in the circulation of IOI patients and decreased (HLA-DR+CD11c+CD1c+) conventional dendritic cells (cDC) type-2 for IOI patients were replicated in an independent cohort of patients and controls. Meta-analysis of both cohorts demonstrated that pDCs are also decreased in blood of NHOL patients and highlighted that the decrease in blood cDC type-2 was specific for IOI patients compared to NHOL or controls. Deconvolution-based estimation of immune cells in transcriptomic data of 48 orbital biopsies revealed a decrease in the abundance of pDC and cDC populations within the orbital microenvironment of IOI patients. Collectively, these data suggest a previously underappreciated role for dendritic cells in orbital disorders.
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Keywords: cDC2, FlowSOM, idiopathic orbital inflammation, non-Hodgkin orbital lymphoma, plasmacytoid dendritic cells, Immunology and Allergy, Immunology, Journal Article
ISSN: 0014-2980
Publisher: Wiley-VCH Verlag
Note: Funding Information: We would like to thank Maarten Mourits and Stijn Genders for their assistance in the recruitment of patients. This study was supported by unrestricted grants from the Dr. F.P Fischerstichting, Stichting Lijf & Leven, Rotterdamse Stichting Blindenbelangen, and Stichting Ankie Hak. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We would like to thank Maarten Mourits and Stijn Genders for their assistance in the recruitment of patients. This study was supported by unrestricted grants from the Dr. F.P Fischerstichting, Stichting Lijf & Leven, Rotterdamse Stichting Blindenbelangen, and Stichting Ankie Hak. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2019 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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