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Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways
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Journal Article
Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways
2025
Overview
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.
Castleman disease encompasses a group of disorders characterised by abnormal lymph node morphology. Here the authors use single cell and spatial transcriptomics to assess the stromal, immune and interaction architecture of different subtypes of Castleman disease, indicating potential ligand-receptor interactions between immune cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/63
/ 38/23
/ 38/91
/ 45
/ 82/51
/ Adult
/ Aged
/ Anemia
/ Castleman Disease - genetics
/ Castleman Disease - immunology
/ Castleman Disease - metabolism
/ Castleman Disease - pathology
/ Cells
/ Chemokine CXCL13 - metabolism
/ Dendritic Cells, Follicular - immunology
/ Dendritic Cells, Follicular - metabolism
/ Dendritic Cells, Follicular - pathology
/ Female
/ Fever
/ HIV
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Male
/ Plasma
/ Science
/ Single-Cell Analysis - methods
/ Vascular endothelial growth factor
