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scRNA‐seq reveals the landscape of immune repertoire of PBMNCs in iMCD

Oncogene volume 43, pages 2795–2805 (2024)Cite this article

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Abstract

The etiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood, and the identification of targetable disease mediators remains an unmet clinical need. Thus, we firstly employed single-cell RNA sequencing (scRNA-seq) to elucidate the landscape of the immune repertoire of peripheral blood mononuclear cells (PBMNCs) in iMCD and to identify additional driver cytokines/cells/pathways to address IL-6 blockade-refractory cases. We revealed that the inflammatory cytokine storm observed in iMCD was a significant phenomenon pervasive across all immune cells. B-plasma cell subsets was the main source of IL-6. The IL-6 signaling pathway was significantly activated across a spectrum of immune cells. Systemic upregulation of CXCL13 is mainly driven by peripheral helper T (Tph) and regulatory T (Treg) cells. Notably, a significant positive interaction was observed between CXCL13-expressing T cells and IL‐6 signaling-activated B cells. This study provides an immune perspective on PBMNCs in iMCD at the single-cell level, unveiling pathways or targets characterized by atypical inflammatory expression that could potentially serve as promising candidates for therapeutic intervention in iMCD.

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Fig. 1: Identifying the infiltrated cell types in iMCD and NC.
Fig. 2: Inflammatory score and cellular composition of B-plasma cells in iMCD and NC.
Fig. 3: Composition analysis of NK-T and myeloid cells in iMCD and NC.
Fig. 4: IL-6 signaling activation in iMCD.
Fig. 5: CXCL13/CXCR5 Interaction is critical in iMCD.
Fig. 6: The cell-cell interactions in specific pathways.

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Data availability

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation to any qualified researcher.

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Acknowledgements

We thank the patients newly diagnosed with iMCD volunteers for their peripheral blood samples and the medical staff of the Department of Hematology, First Affiliated Hospital, College of Medicine, Zhejiang University. We thank OE Biotech Co., Ltd (Shanghai, China) for providing single-cell RNA-seq. We thank Zhenbo Wang of the Cosmos Wisdom Biotech Co., Ltd. (Hangzhou, China) for analyzing the data. We thank Cosmos Wisdom Biotech Co., Ltd. (Hangzhou, China) for providing single-cell related services.

Funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LZ23H080002 and LQ24H080005) and the National Natural Science Foundation of China (Grant No.82100241).

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Author notes

  1. These authors contributed equally: Xuejiao Yin, Yi Liu.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Xuejiao Yin, Yi Liu, Shengnan Ding, Liya Ma, Min Yang, Meiqiu Yao, Li Zhu, Shuqi Zhao, Yu Chen, Jiaying Ge, Hongyan Tong, Haitao Meng & Liangshun You

  2. Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou, Zhejiang, China

    Xuejiao Yin, Yi Liu, Shengnan Ding, Liya Ma, Min Yang, Meiqiu Yao, Li Zhu, Hongyan Tong, Haitao Meng & Liangshun You

  3. Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou, Zhejiang, China

    Xuejiao Yin, Yi Liu, Yu Chen, Hongyan Tong, Haitao Meng & Liangshun You

  4. Zhejiang University Cancer Center, Hangzhou, Zhejiang, China

    Xuejiao Yin, Hongyan Tong, Haitao Meng & Liangshun You

  5. Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China

    Zuopo Lv

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  1. Xuejiao Yin
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Contributions

LSY, HYT and HTM designed the study. LSY, YL and XJY performed the research and analyzed the data. LSY and XJY wrote the manuscript. SND, ZPL, LYM, MY, MQY, LZ, SQZ, YC and JYG reviewed and edited the manuscript. All authors participated in drafting the manuscript and approved the final version.

Corresponding authors

Correspondence to Hongyan Tong, Haitao Meng or Liangshun You.

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The authors declare no competing interests.

Ethics approval

Studies involving human participants were reviewed and approved by the independent Ethics Committee of The First Affiliated Hospital, College of Medicine, Zhejiang University. The patients provided written informed consent to participate in the study. This research was performed in accordance with the principles of the Declaration of Helsinki.

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Yin, X., Liu, Y., Lv, Z. et al. scRNA‐seq reveals the landscape of immune repertoire of PBMNCs in iMCD. Oncogene 43, 2795–2805 (2024). https://doi.org/10.1038/s41388-024-03128-8

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