Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways
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 show...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61214-1 |
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| author | 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 Katherine J. Young Paul G. Murray Christopher Park Boris Reizis Vinodh Pillai |
| author_facet | 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 Katherine J. Young Paul G. Murray Christopher Park Boris Reizis Vinodh Pillai |
| author_sort | David Smith |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dba0068b24c445d8960ea1167ade7b61 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dba0068b24c445d8960ea1167ade7b612025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-61214-1Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathwaysDavid Smith0Anna Eichinger1Éanna Fennell2Zijun Y. Xu-Monette3Andrew Rech4Julia Wang5Eduardo Esteva6Arta Seyedian7Xiaoxu Yang8Mei Zhang9Dan Martinez10Kai Tan11Minjie Luo12Katherine J. Young13Paul G. Murray14Christopher Park15Boris Reizis16Vinodh Pillai17Center for Single Cell Biology, Children’s Hospital of Philadelphia Research InstituteDepartment of Pathology, New York University Grossman School of MedicineSchool of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of LimerickDuke University Medical CenterDepartment of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia and the University of PennsylvaniaDepartment of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia and the University of PennsylvaniaDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pediatrics, The Children’s Hospital of PhiladelphiaCenter for Single Cell Biology, Children’s Hospital of Philadelphia Research InstituteCenter for Single Cell Biology, Children’s Hospital of Philadelphia Research InstituteSchool of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of LimerickCenter for Single Cell Biology, Children’s Hospital of Philadelphia Research InstituteSchool of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of LimerickDuke University Medical CenterSchool of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of LimerickDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology, New York University Grossman School of MedicineDepartment of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia and the University of PennsylvaniaAbstract 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.https://doi.org/10.1038/s41467-025-61214-1 |
| spellingShingle | 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 Katherine J. Young Paul G. Murray Christopher Park Boris Reizis Vinodh Pillai Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways Nature Communications |
| title | Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| title_full | Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| title_fullStr | Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| title_full_unstemmed | Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| title_short | Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| title_sort | spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways |
| url | https://doi.org/10.1038/s41467-025-61214-1 |
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