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ACPA-CD147 axis in the NLRP3 inflammasome of RA macrophages

Cellular & Molecular Immunology volume 19, pages 957–959 (2022)Cite this article

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In a recent publication in Cellular and Molecular Immunology, DONG et al. present new data from rheumatoid arthritis (RA) patients with or without anti-citrullinated peptide/protein antibodies (ACPAs), linking the ACPA-CD147 axis in macrophages to the inflammasome-related pathogenesis of this disease [1]. In this commentary, the findings regarding the ACPA-CD147 axis will be discussed, with accumulating evidence for the important roles of macrophage inflammasomes in RA pathogenesis.

Inflammasomes can trigger inflammatory cascades and the subsequent specific immunity of autoimmune diseases, including RA, gout, and systemic lupus erythematosus. Among the inflammasome-related NOD-like receptor (NLR) family subsets, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) may be the most studied subtype in monocytes and macrophages, especially in RA [2,3,4]. As important components of innate immunity, monocytes and macrophages play fundamental roles in RA pathophysiology, and the dysfunction of NLRP3 on these cells has been verified. In our study, NLRP3 induced IL-1β expression mainly in monocytes and macrophages of RA synovial tissue, and this expression was higher than in osteoarthritis synovial tissue; moreover, this induced expression was higher in ACPA-positive patients than in ACPA-negative patients. Then, macrophages derived from peripheral blood mononuclear cells were stimulated by the ACPA-CD147 axis, and IL-1β production was proven to be NLRP3-dependent [1]. In RA monocytes/macrophages, various NLRP3 activation pathways have been found, and more potent targets need to be identified and verified.

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Acknowledgements

This study was funded by the National Natural Science Foundation of China (81871273) and the Major Research Plan of National Natural Science Foundation of China (92169211).

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  1. These authors contributed equally: Kui Zhang, Yan Zheng, Zhaohui Zheng.

Authors and Affiliations

  1. Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, PR China

    Kui Zhang, Yan Zheng, Zhaohui Zheng & Ping Zhu

  2. National Translational Science Center for Molecular Medicine, Xi’an, Shaanxi, PR China

    Kui Zhang, Yan Zheng, Zhaohui Zheng & Ping Zhu

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  1. Kui Zhang
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  2. Yan Zheng
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Contributions

KZ and ZZ contributed to the completion of the first draft and final version of the manuscript. YZ contributed to the data acquisition and diagramming. PZ contributed to the initial design of the work. All authors contributed to the article and approved the submitted version.

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Correspondence to Ping Zhu.

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The authors declare no competing interests.

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Zhang, K., Zheng, Y., Zheng, Z. et al. ACPA-CD147 axis in the NLRP3 inflammasome of RA macrophages. Cell Mol Immunol 19, 957–959 (2022). https://doi.org/10.1038/s41423-022-00889-8

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