Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell
Amy J Petty1, Adela Rambi Cardones1,2, Yingai Jane Jin1
1Department of Dermatology, Duke University, Durham, North Carolina, USA.
Summary
Skin cells and immune cells show unique changes in chronic graft-versus-host disease (GVHD). Understanding these cutaneous GVHD alterations is key for developing targeted skin treatments.
Area of Science:
- Immunology
- Dermatology
- Genomics
Background:
- Cutaneous manifestations are common in chronic graft-versus-host disease (GVHD), impacting prognosis.
- The pathogenesis of skin injury in chronic GVHD, particularly the role of structural skin cells, remains poorly understood.
Purpose of the Study:
- To investigate the molecular changes in epidermal and dermal cells during chronic GVHD.
- To compare the transcriptomes of cells from chronic GVHD skin lesions with healthy controls.
Main Methods:
- Single-cell RNA sequencing was employed to analyze epidermal and dermal samples.
- Transcriptomic profiles of chronic GVHD and healthy control skin were compared.
Main Results:
- Epidermal keratinocytes showed altered expression of inflammatory and antioxidant genes.
- Dermal immune cells, including T cells and NK cells, were increased, with heightened inflammatory and cytolytic activity.
- Donor versus recipient cell origins were identified in sex-mismatched chronic GVHD.
Conclusions:
- Cutaneous chronic GVHD involves complex, non-immunologic and immunologic changes in skin cells.
- These findings highlight the contribution of structural skin cells to chronic GVHD pathogenesis.
- Further research into skin cell roles may lead to novel, localized treatment strategies.
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