Cell Reports (May 2023)
Tissue-resident, extravascular Ly6c− monocytes are critical for inflammation in the synovium
- Anna B. Montgomery,
- Shang Yang Chen,
- Yidan Wang,
- Gaurav Gadhvi,
- Maximilian G. Mayr,
- Carla M. Cuda,
- Salina Dominguez,
- Hadijat-Kubura Moradeke Makinde,
- Miranda G. Gurra,
- Alexander V. Misharin,
- Arthur M. Mandelin,
- Eric M. Ruderman,
- Anjali Thakrar,
- Simran Brar,
- Mary Carns,
- Kathleen Aren,
- Mahzad Akbarpour,
- Andrew Filer,
- Saba Nayar,
- Ana Teososio,
- Triin Major,
- Ankit Bharat,
- G.R. Scott Budinger,
- Deborah R. Winter,
- Harris Perlman
Affiliations
- Anna B. Montgomery
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Shang Yang Chen
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Yidan Wang
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Gaurav Gadhvi
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Maximilian G. Mayr
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Carla M. Cuda
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Salina Dominguez
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Hadijat-Kubura Moradeke Makinde
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Miranda G. Gurra
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Alexander V. Misharin
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care, Chicago, IL 60611, USA
- Arthur M. Mandelin
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Eric M. Ruderman
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Anjali Thakrar
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Simran Brar
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Mary Carns
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Kathleen Aren
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA
- Mahzad Akbarpour
- Northwestern University, Feinberg School of Medicine, Division of Thoracic Surgery, Chicago, IL 60611, USA
- Andrew Filer
- Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Saba Nayar
- Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Ana Teososio
- Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Triin Major
- Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Ankit Bharat
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care, Chicago, IL 60611, USA; Northwestern University, Feinberg School of Medicine, Division of Thoracic Surgery, Chicago, IL 60611, USA
- G.R. Scott Budinger
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care, Chicago, IL 60611, USA
- Deborah R. Winter
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA; Corresponding author
- Harris Perlman
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 5
p. 112513
Abstract
Summary: Monocytes are abundant immune cells that infiltrate inflamed organs. However, the majority of monocyte studies focus on circulating cells, rather than those in tissue. Here, we identify and characterize an intravascular synovial monocyte population resembling circulating non-classical monocytes and an extravascular tissue-resident monocyte-lineage cell (TR-MC) population distinct in surface marker and transcriptional profile from circulating monocytes, dendritic cells, and tissue macrophages that are conserved in rheumatoid arthritis (RA) patients. TR-MCs are independent of NR4A1 and CCR2, long lived, and embryonically derived. TR-MCs undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. Moreover, pathways that are activated in TR-MCs at the peak of arthritis overlap with those that are downregulated in LFA1−/− TR-MCs. These findings show a facet of mononuclear cell biology that could be imperative to understanding tissue-resident myeloid cell function in RA.
