Molecular Medicine (Jun 2022)

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms

  • Jiali Ni,
  • Haiyan Zhu,
  • Li Lu,
  • Zihe Zhao,
  • Jiaxuan Jiang,
  • Xiaokang You,
  • Yuzhu Wang,
  • Yuliang Ma,
  • Zirui Yang,
  • Yayi Hou,
  • Huan Dou

DOI
https://doi.org/10.1186/s10020-022-00493-6
Journal volume & issue
Vol. 28, no. 1
pp. 1 – 15

Abstract

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Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. Hydroxychloroquine (HCQ) has been used clinically to treat SLE, while its exact mechanism has still remained elusive. Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation of SLE. In this study, we aimed to explore the effects of HCQ on the apoptosis of MDSCs in lupus mice and its possible molecular regulatory mechanism. Methods We constructed the imiquimod (IMQ)-induced lupus model in mice. The proportion and apoptosis of MDSCs were measured by flow cytometry. CD81-overexpressed adeno-associated virus was intraperitoneally injected into the lupus mice. We also transfected the CD81 siRNA into bone marrow-derived MDSCs, and employed qRT-PCR and Western blotting to quantify the level of CD81. Results The results showed that HCQ ameliorated IMQ-induced lupus symptoms, and simultaneously inhibited the expansion of MDSCs. In particular, HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs. CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression by overexpressing CD81 in vivo. Molecular docking experiment further proved the targeting effect of HCQ on CD81. And then we interfered CD81 in bone marrow derived MDSCs in vitro, and it was revealed that HCQ rescued the decreased expression level of CD81 and relieved the immune imbalance of Th17/Treg cells. Conclusion In summary, HCQ promoted the apoptosis of MDSCs by up-regulating the expression level of CD81 in MDSCs, and ultimately alleviated lupus symptoms. Our results may assist scholars to develop further effective therapies for SLE.

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