Tissue-resident, extravascular Ly6c monocytes are critical for inflammation in the synovium.
Montgomery, Anna B Chen, Shang Yang Wang, Yidan Gadhvi, Gaurav Mayr, Maximilian G Cuda, Carla M Dominguez, Salina Moradeke Makinde, Hadijat-Kubura Gurra, Miranda G Misharin, Alexander V
Montgomery, Anna B
Chen, Shang Yang
Wang, Yidan
Gadhvi, Gaurav
Mayr, Maximilian G
Cuda, Carla M
Dominguez, Salina
Moradeke Makinde, Hadijat-Kubura
Gurra, Miranda G
Misharin, Alexander V
Citations
Altmetric:
Affiliation
Other Contributors
Publication date
2023-05-18
Collections
Research Projects
Organizational Units
Journal Issue
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.
Citation
Montgomery AB, Chen SY, Wang Y, Gadhvi G, Mayr MG, Cuda CM, Dominguez S, Moradeke Makinde HK, Gurra MG, Misharin AV, Mandelin AM, Ruderman EM, Thakrar A, Brar S, Carns M, Aren K, Akbarpour M, Filer A, Nayar S, Teososio A, Major T, Bharat A, Budinger GRS, Winter DR, Perlman H. 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.
Type
Article