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.
Original language | English |
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Article number | 112513 |
Number of pages | 25 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 5 |
Early online date | 18 May 2023 |
DOIs | |
Publication status | Published - 30 May 2023 |
Bibliographical note
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.Acknowledgments
We would like to thank Dr. Steffen Jung for providing critical review of the manuscript. We would also like to thank the Northwestern University Lurie Cancer Center Flow Cytometry Core Facility, which is supported by NCI Cancer Center Support Grant P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center; Dr. Hiam Abdala Valencia, Director of the Next Generation Sequencing Facility for the Divisions of Rheumatology/Pulmonary and Critical Care; the Northwestern NUSeq Core Facility; and Birmingham Tissue Analytics, University of Birmingham, UK. This research was supported in part through the computational resources and staff contributions provided by the Genomics Compute Cluster, which is jointly supported by the Feinberg School of Medicine, the Office of the Provost, the Office for Research, and Northwestern Information Technology. The Genomics Compute Cluster is part of Quest, Northwestern University’s high-performance computing facility, with the purpose to advance research in genomics. S.Y.C. was supported by a predoctoral AHA award (19PRE34380200). C.M.C. was supported by the Lupus Research Alliance (Novel Research Grant), the Rheumatology Research Foundation (Innovative Research Grant), and the Northwestern University Dixon Translational Research Initiative. H.-K.M.M. was supported by KL2 TR001424, HL134375S1, and AR007611. A.V.M. was supported by NIH grants U19AI135964, P01AG049665, PO1HL154998, R56HL135124, R01HL153312, and NUCATS COVID-19 Rapid Response Grant. A.B. was supported by NIH grants HL145478, HL147290, and HL147575. G.R.S.B. was supported by NIH grants U19AI135964, P01AG049665, P01AG04966506S1, and R01HL147575 and Veterans Affairs grant I01CX001777. D.R.W. was supported by funding from the Arthritis National Research Foundation, the American Federation for Aging Research, the American Heart Association (18CDA34110224), and NIH grants AI163742 and AR080513. H.P. was supported by AR074902, AR075423, CA060553, HL134375, AR080513, an RRF Innovative Research Grant, a United States-Israel Binational Science Foundation Investigator Grant, the Precision Medicine Fund, and the Mabel Green Myers Professorship.
Keywords
- Humans
- Monocytes/metabolism
- Synovial Membrane
- Arthritis, Rheumatoid
- Inflammation/metabolism