ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1627389
Exosome circ-CBLB promotes M1 macrophage polarization in rheumatoid arthritis through the TLR3/TRAF3 signaling axis
Provisionally accepted
- 1Anhui University of Traditional Chinese Medicine First Clinical Medical College, HeFei, China
- 2First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, HeFei, China
- 3Anhui University of Traditional Chinese Medicine Academic Affairs Office, HeFei, China
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Background： Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by persistent inflammation of the joint's synovial membrane. This inflammation leads to the degradation of joint cartilage and bone, resulting in joint dysfunction and deformity. Early symptoms of RA are often subtle, complicating timely diagnosis. Identifying potential markers for RA is therefore critical.This study aimed to explore the role of circular RNA CBLB (circ-CBLB) in RA by examining its influence on the Toll-like receptor 3/TNF receptor-associated factor 3 (TLR3/TRAF3) signaling axis and its effects on macrophage polarization through exosomes.Results：We found that exosomes may contribute to macrophage polarization, as shown through exosome uptake assays and flow cytometry. Clinical data reveal low expression levels of circ-CBLB in rheumatoid arthritis patients, correlating negatively with immunoinflammatory indices. Overexpression of circ-CBLB was found to inhibit M1 macrophage polarization. Further, binding between circ-CBLB and TLR3 was confirmed using RNA Immunoprecipitation, RNA pulldown, Western blot analysis, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques. Inhibiting circ-CBLB or TLR3 demonstrated that the effects on macrophage polarization could be counteracted by introducing inhibitors or inducers for M2 macrophage polarization, underscoring the significant role of exosomal circ-CBLB in RA.Exosomal circ-CBLB plays a crucial role in inhibiting the TLR3/TRAF3 signaling pathway, thereby reducing M1 macrophage polarization in RA patients. These findings enhance our understanding of pathophysiology of RA and offer novel insights and methods for its diagnosis and treatment.Rheumatoid Arthritis (RA) is a common autoimmune disease characterized by symptoms such as joint pain, swelling, stiffness, and deformity, and it can also affect multiple organ systems including the cardiovascular and respiratory systems, and the eyes, significantly impairing patient quality of life [1][2][3][4]. The chronic nature of RA necessitates long-term treatment and management,
Keywords: CBLB, TLR ( Toll like receptors), Rheumatoid arthritis, Macrophage - cell, circRNA, TRAF3, immune inflammation
Received: 12 May 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Zhang, Wan, Zhang, Wang, Li and YAN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mengyu Zhang, Anhui University of Traditional Chinese Medicine First Clinical Medical College, HeFei, China
Lei Wan, Anhui University of Traditional Chinese Medicine First Clinical Medical College, HeFei, China
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