Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics
Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpinning injury at this location, especially the...
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Elsevier
2025-07-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000293 |
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| author | Amy J. Petty Adela Rambi Cardones Yingai Jane Jin Vaibhav Jain Emily Hocke Harsh B. Pathak Amrita Mitra Simon G. Gregory M. Angelica Selim Jennifer Y. Zhang |
| author_facet | Amy J. Petty Adela Rambi Cardones Yingai Jane Jin Vaibhav Jain Emily Hocke Harsh B. Pathak Amrita Mitra Simon G. Gregory M. Angelica Selim Jennifer Y. Zhang |
| author_sort | Amy J. Petty |
| collection | DOAJ |
| description | Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpinning injury at this location, especially the contribution of keratinocytes and other structural skin cells. We performed single-cell RNA sequencing to compare the transcriptome of epidermal and dermal chronic GVHD samples with that of healthy control samples. Our findings reveal unique nonimmunologic and immunologic changes in epidermal keratinocytes and dermal immune cells. Specifically, we observed upregulation of alarmins and inflammatory cytokines and downregulation of anti-reduction–oxidation and activator protein-1 pathway genes in the keratinocyte compartments. In dermal immune cell subsets, we showed increased CD8+ T, CD4+ T, CD4+Foxp3+ regulatory T, and NK cells in chronic GVHD, accompanied by increased signals of leukocyte functions, inflammatory responses, cytolysis, and macrophage M1 polarization. Finally, we also delineated the donor versus recipient cellular origin of nonimmune and immune cell populations in sex-mismatched chronic GVHD. Taken together, these data reveal complex keratinocyte and immune responses in cutaneous chronic GVHD, supporting future studies of skin cell contributions to pathogenesis and potential local treatment strategies. |
| format | Article |
| id | doaj-art-43116e8131f74cf18e13acfebc2eb9ee |
| institution | Kabale University |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-43116e8131f74cf18e13acfebc2eb9ee2025-08-20T03:34:00ZengElsevierJID Innovations2667-02672025-07-015410037310.1016/j.xjidi.2025.100373Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell TranscriptomicsAmy J. Petty0Adela Rambi Cardones1Yingai Jane Jin2Vaibhav Jain3Emily Hocke4Harsh B. Pathak5Amrita Mitra6Simon G. Gregory7M. Angelica Selim8Jennifer Y. Zhang9Department of Dermatology, Duke University, Durham, North Carolina, USADepartment of Dermatology, Duke University, Durham, North Carolina, USA; Division of Dermatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USADepartment of Dermatology, Duke University, Durham, North Carolina, USAMolecular Genomic Core, Duke University, Durham, North Carolina, USAMolecular Genomic Core, Duke University, Durham, North Carolina, USADepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USADepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USAMolecular Genomic Core, Duke University, Durham, North Carolina, USA; Department of Neurosurgery, Duke University, Durham, North Carolina, USADepartment of Pathology, Duke University, Durham, North Carolina, USADepartment of Dermatology, Duke University, Durham, North Carolina, USA; Department of Pathology, Duke University, Durham, North Carolina, USA; Correspondence: Jennifer Y. Zhang, Department of Dermatology, Duke University, 200 Trent Drive, Durham, North Carolina 27710, USA.Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpinning injury at this location, especially the contribution of keratinocytes and other structural skin cells. We performed single-cell RNA sequencing to compare the transcriptome of epidermal and dermal chronic GVHD samples with that of healthy control samples. Our findings reveal unique nonimmunologic and immunologic changes in epidermal keratinocytes and dermal immune cells. Specifically, we observed upregulation of alarmins and inflammatory cytokines and downregulation of anti-reduction–oxidation and activator protein-1 pathway genes in the keratinocyte compartments. In dermal immune cell subsets, we showed increased CD8+ T, CD4+ T, CD4+Foxp3+ regulatory T, and NK cells in chronic GVHD, accompanied by increased signals of leukocyte functions, inflammatory responses, cytolysis, and macrophage M1 polarization. Finally, we also delineated the donor versus recipient cellular origin of nonimmune and immune cell populations in sex-mismatched chronic GVHD. Taken together, these data reveal complex keratinocyte and immune responses in cutaneous chronic GVHD, supporting future studies of skin cell contributions to pathogenesis and potential local treatment strategies.http://www.sciencedirect.com/science/article/pii/S2667026725000293Cutaneous chronic GVHDGraft-versus-host diseaseKeratinocytesM1 and M2 macrophagesT cells |
| spellingShingle | Amy J. Petty Adela Rambi Cardones Yingai Jane Jin Vaibhav Jain Emily Hocke Harsh B. Pathak Amrita Mitra Simon G. Gregory M. Angelica Selim Jennifer Y. Zhang Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics JID Innovations Cutaneous chronic GVHD Graft-versus-host disease Keratinocytes M1 and M2 macrophages T cells |
| title | Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics |
| title_full | Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics |
| title_fullStr | Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics |
| title_full_unstemmed | Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics |
| title_short | Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics |
| title_sort | insights into keratinocyte and immunologic landscape in cutaneous graft versus host disease through single cell transcriptomics |
| topic | Cutaneous chronic GVHD Graft-versus-host disease Keratinocytes M1 and M2 macrophages T cells |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000293 |
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