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Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways

Author

Listed:
  • David Smith

    (Children’s Hospital of Philadelphia Research Institute)

  • Anna Eichinger

    (New York University Grossman School of Medicine
    Ludwig-Maximilians-Universität München)

  • Éanna Fennell

    (University of Limerick)

  • Zijun Y. Xu-Monette

    (Duke University Medical Center)

  • Andrew Rech

    (The Children’s Hospital of Philadelphia and the University of Pennsylvania)

  • Julia Wang

    (The Children’s Hospital of Philadelphia and the University of Pennsylvania)

  • Eduardo Esteva

    (New York University Grossman School of Medicine)

  • Arta Seyedian

    (The Children’s Hospital of Philadelphia)

  • Xiaoxu Yang

    (Children’s Hospital of Philadelphia Research Institute)

  • Mei Zhang

    (Children’s Hospital of Philadelphia Research Institute)

  • Dan Martinez

    (University of Limerick)

  • Kai Tan

    (Children’s Hospital of Philadelphia Research Institute
    The Children’s Hospital of Philadelphia)

  • Minjie Luo

    (University of Limerick)

  • Katherine J. Young

    (Duke University Medical Center)

  • Paul G. Murray

    (University of Limerick)

  • Christopher Park

    (New York University Grossman School of Medicine)

  • Boris Reizis

    (New York University Grossman School of Medicine)

  • Vinodh Pillai

    (The Children’s Hospital of Philadelphia and the University of Pennsylvania)

Abstract

To determine the cellular and molecular basis of Castleman Disease (CD), we analyze the spatial proteome and transcriptome from a discovery (n = 9 cases) and validation (n = 13 cases) cohort of Unicentric CD, idiopathic Multicentric CD, HHV8-associated MCD, and reactive lymph nodes. CD shows increased stromal cells that form unique microenvironments. Interaction of activated follicular dendritic cell (FDC) cytoplasmic meshworks with mantle-zone B cells is associated with B-cell activation and differentiation. CXCL13+ FDCs, PDGFRA + T-zone reticular cells (TRC), and ACTA2-positive perivascular reticular cells (PRC) were the predominant source of increased VEGF expression and IL-6 signaling. MCD is characterized by increased TRC while UCD shows increased B-reticular cells (BRC). VEGF expression by FDCs is associated with peri-follicular neovascularization. FDC, TRC and PRC of CD activates JAK-STAT, TGFβ, and MAPK pathways via specific ligand-receptor interactions. Here, we show that stromal-cell activation and associated B cell activation and differentiation, neovascularization and stromal remodeling underlie CD.

Suggested Citation

  • David Smith & Anna Eichinger & Éanna Fennell & Zijun Y. Xu-Monette & Andrew Rech & Julia Wang & Eduardo Esteva & Arta Seyedian & Xiaoxu Yang & Mei Zhang & Dan Martinez & Kai Tan & Minjie Luo & Katheri, 2025. "Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61214-1
    DOI: 10.1038/s41467-025-61214-1
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    References listed on IDEAS

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