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

doi:10.1016/j.celrep.2023.112513

Tissue-resident, extravascular Ly6c^- monocytes are critical for inflammation in the synovium

Cell Rep. 2023 May 30;42(5):112513. doi: 10.1016/j.celrep.2023.112513. Epub 2023 May 18.

Authors

Anna B Montgomery¹, Shang Yang Chen¹, Yidan Wang¹, Gaurav Gadhvi¹, Maximilian G Mayr¹, Carla M Cuda¹, Salina Dominguez¹, Hadijat-Kubura Moradeke Makinde¹, Miranda G Gurra¹, Alexander V Misharin², Arthur M Mandelin¹, Eric M Ruderman¹, Anjali Thakrar¹, Simran Brar¹, Mary Carns¹, Kathleen Aren¹, Mahzad Akbarpour³, Andrew Filer⁴, Saba Nayar⁴, Ana Teososio⁵, Triin Major⁵, Ankit Bharat⁶, G R Scott Budinger², Deborah R Winter⁷, Harris Perlman⁸

Affiliations

¹ Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA.
² Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care, Chicago, IL 60611, USA.
³ Northwestern University, Feinberg School of Medicine, Division of Thoracic Surgery, Chicago, IL 60611, USA.
⁴ 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.
⁵ Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK.
⁶ 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.
⁷ Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA. Electronic address: deborah.winter@northwestern.edu.
⁸ Northwestern University, Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, Chicago, IL 60611, USA. Electronic address: h-perlman@northwestern.edu.

Abstract

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.

Keywords: CP: Immunology; arthritis; macrophages; monoyctes.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid*
Humans
Inflammation / metabolism
Monocytes* / metabolism
Synovial Membrane

Abstract

Publication types

MeSH terms

Grants and funding