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Upregulation of CD39 During Gout Attacks Promotes Spontaneous Remission of Acute Gouty Inflammation

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Abstract

Gout is a self-limiting form of inflammatory arthropathy caused by the formation of urate crystals due to hyperuricemia. The resolution of gout involves the transition of proinflammatory M1-type macrophages to anti-inflammatory M2-type macrophages, as well as neutrophil-mediated extracellular trap (NET) formation. However, the underlying mechanisms of these changes are not clear. Studies have confirmed that high expression of CD39 on macrophages and neutrophils can trigger the polarization of macrophages from a proinflammatory state to an anti-inflammatory state. Recent studies have shown that the pathogenesis of gout involves extracellular ATP (eATP), and the synergistic effect of MSU and extracellular ATP can cause gout. CD39 is a kind of ATP hydrolysis enzyme that can degrade eATP, suggesting that CD39 may inhibit the aggravation of inflammation in gout and participate in the remission mechanism of gout. To confirm this hypothesis, using data mining and flow cytometry, we first found that CD39 expression was significantly upregulated on CD14 + monocytes and neutrophils in gout patients during the acute phase. Inhibition of CD39 by lentivirus or a CD39 inhibitor in acute gout models aggravated gouty arthritis and delayed gout remission. Apyrase, a functional analog of CD39, can significantly reduce the inflammatory response and promote gout remission in acute gout model mice. Our findings confirm that the upregulation of CD39 during gout flare-ups promotes spontaneous remission of acute gouty inflammation.

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Data Availability

The data presented in this study are available upon request from the corresponding author.

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Acknowledgements

We thank Yujie Tang, Hongliang Zhang, and Yuting Li for their technical help.

Funding

This work was supported by the Fundamental Research Funds for the Central Universities (YD9110002017).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, 230001, People’s Republic of China

    Chengyu Luo, Xingyue Liu, Yiming Liu, Jie Gao & Jinhui Tao

  2. Department of Rheumatology and Immunology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, 230001, People’s Republic of China

    Huijun Shao & Jinhui Tao

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  1. Chengyu Luo
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Contributions

JT and CL contributed to the conception and design of the study. CL, XL, YL, JG and HS conducted the experiments and analyzed the data. CL drafted the manuscript. All authors contributed to manuscript revision and approved the submitted version.

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Correspondence to Jinhui Tao.

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Our protocols for the collection and processing of animal and human samples were approved by the Animal Ethics Committee (2021-N(A)-041) and Medical Research Ethics Committee (2021 KY No.162) of the First Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), respectively. All persons gave their informed consent before their inclusion in the study.

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Luo, C., Liu, X., Liu, Y. et al. Upregulation of CD39 During Gout Attacks Promotes Spontaneous Remission of Acute Gouty Inflammation. Inflammation 47, 664–677 (2024). https://doi.org/10.1007/s10753-023-01936-w

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