Abstract
Vitamin D promotes a shift from a proinflammatory to a more tolerogenic immune state in allogeneic hematopoietic cell transplant (HCT) recipients. The dominant mechanism responsible for this shift has not been elucidated. We took a multifaceted approach to evaluating the clinical and immunologic impact of low vitamin D levels in 53 HCT recipients. We used 28-plex flow cytometry for immunophenotyping, serum cytokine levels, T-cell cytokine production, and T-cell whole genome transcription. The median day-30 vitamin D level was 20 ng/mL, and deficiency was common in younger patients undergoing myeloablative transplantation. Low vitamin D levels were associated with a high CD8/Treg ratio, increased serum levels and T-cell production of proinflammatory cytokines, and a gene expression signature of unrestrained T-cell proliferation and epigenetic modulation through the PRC2/EZH2 complex. Immunophenotyping confirmed a strong association between high levels of vitamin D and an activated EZH2 signature, characterized by overexpression of ID3, which has a role in effector T-cell differentiation. Our findings demonstrate the critical role of vitamin D in modulating T-cell function in human GVHD and identify a previously undescribed interaction with EZH2 and ID3, which may impact effector differentiation and has implications to cell therapies and other forms of cancer immunotherapy.
Original language | English (US) |
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Pages (from-to) | 18.e1-18.e10 |
Journal | Transplantation and Cellular Therapy |
Volume | 28 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2022 |
Externally published | Yes |
Keywords
- Acute graft-versus-host disease
- Allogeneic hematopoietic cell transplantation
- Epigenetic regulation
- T-cell function
- Vitamin D
ASJC Scopus subject areas
- Immunology and Allergy
- Molecular Medicine
- Hematology
- Cell Biology
- Transplantation