cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non-Hodgkin orbital lymphoma and idiopathic orbital inflammation

Kamil G. Laban*, Rianne Rijken, Sanne Hiddingh, Jorre S. Mertens, Rob L.P. van der Veen, Christine A.E. Eenhorst, Aridaman Pandit, Timothy R.D.J. Radstake, Joke H. de Boer, Rachel Kalmann, Jonas J.W. Kuiper

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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. 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.

Original languageEnglish
Pages (from-to)548-557
Number of pages10
JournalEuropean Journal of Immunology
Volume50
Issue number4
DOIs
Publication statusPublished - Apr 2020

Keywords

  • cDC2
  • FlowSOM
  • idiopathic orbital inflammation
  • non-Hodgkin orbital lymphoma
  • plasmacytoid dendritic cells

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