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Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α + B cells through BAFF/BTK/NF-B signaling pathway in the pathogenesis of collagen-induced arthritis mice
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  • Mei Li,
  • Zhicheng Tang,
  • Haolin Wu,
  • Yue Wang,
  • Ziyan Chen,
  • Zixue cheng,
  • Xinyi Yan,
  • Nan Zhao,
  • Xiaojun Tang,
  • Huayong Zhang,
  • Lingyun Sun
Mei Li
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Zhicheng Tang
Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University
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Haolin Wu
Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine
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Yue Wang
Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine
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Ziyan Chen
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Zixue cheng
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Xinyi Yan
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Nan Zhao
Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine
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Xiaojun Tang
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Huayong Zhang
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology

Corresponding Author:[email protected]

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Lingyun Sun
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital Department of Rheumatology and Immunology
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Abstract

Objectives: Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. Methods: We detected the frequencies and counts of PMN-MDSCs, TNF- + B cells, and Ki67 + B cells in spleens and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, etc. The mechanism of BAFF regulating B cells was verified through Western Blot and flow cytometry. Results: PMN-MDSCs accumulated in the spleens and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF- secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF- expression, proliferation and apoptosis of B cells in vitro. What’s more, BAFF promoted phosphorylation of BTK/NF-B signaling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF- expression. Conclusions: Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF- expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF- expression through BTK/NF-B signaling pathway, which demonstrated a novel pathogenesis of PMN-MDSC in CIA.
04 May 20231st Revision Received
12 May 2023Submission Checks Completed
12 May 2023Assigned to Editor
12 May 2023Review(s) Completed, Editorial Evaluation Pending
18 May 2023Editorial Decision: Accept