Full Papers
Synovial resident macrophage-derived PU.1 alleviates rheumatoid arthritis by promoting efferocytosis of fibroblast-like synoviocytes
M. Fu1, Y. Liu2, Y. Jing3, J. Wang4
- Trauma Department of Orthopaedics, Yantaishan Hospital, Yantai, Shandong, China.
- Trauma Department of Orthopaedics, Yantaishan Hospital, Yantai, Shandong, China.
- Trauma Department of Orthopaedics, Yantaishan Hospital, Yantai, Shandong, China.
- Trauma Department of Orthopaedics, Yantaishan Hospital, Yantai, Shandong, China. jianhangwang@yeah.net
CER18839
Full Papers
Received: 16/04/2025
Accepted : 21/04/2026
In Press: 18/06/2026
Abstract
OBJECTIVES:
Spi-1 proto-oncogene (PU.1) is dysregulated in various immune disorders, including rheumatoid arthritis (RA). Herein, we investigate the role of PU.1 in the clearance and degradation of phagolysosomal cargo by synovial resident macrophages in RA.
METHODS:
Collagen-induced arthritis (CIA) was used to establish an RA mouse model. Histological analysis was conducted using haematoxylin and eosin (HE) and safranine O/fast green staining. Macrophage function was determined using flow cytometry and propidium iodide staining assay. Moreover, gene expression was analysed by immunofluorescence, immunohistochemistry, western blot, and reverse transcription-quantitative PCR (RT-qPCR). Cytokine release was detected using enzyme-linked immunosorbent assay (ELISA).
RESULTS:
We found that PU.1 was upregulated in response to RA. PU.1 depletion exacerbated synovial dysfunction, accompanied by the pyroptosis of synovial resident macrophages and the accumulation of dying fibroblast-like synoviocytes (FLS) and inhibition of in vivo efferocytosis. Furthermore, PU.1 deficiency suppressed the formation of LC3-II. Additionally, PU.1 depletion decreased expansion of gelsolin (GSN)+CD86+ cells. Moreover, PU.1 transcriptionally inactivated NLR family pyrin domain containing 3 (NLRP3).
CONCLUSIONS:
Overexpressed PU.1 promoted the proliferation of synovial resident macrophages as well as the clearance of apoptotic FLS in RA. In summary, PU.1-mediated synovial resident macrophage efferocytosis promote tissue repair in RA. Therefore, targeting synovial resident macrophages may a novel strategy for RA.
