Vitamin D deficiency after allogeneic hematopoietic cell transplantation promotes T-cell activation and is inversely associated with an EZH2-ID3 signature
| Autor: | Lee P. Richman, Rodney Macedo, Ran Reshef, Chloé Pasin, Ximi K. Wang, David L. Porter, Alex Ganetsky, Ying Wang, David Harle, Austin P. Huffman, Robert H. Vonderheide, Yi Zhang, Kirubel S Belay, Andrew J. Yates |
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| Rok vydání: | 2022 |
| Předmět: |
Transplantation Conditioning
medicine.medical_treatment T cell Graft vs Host Disease Article vitamin D deficiency Proinflammatory cytokine Immunophenotyping medicine Vitamin D and neurology Humans Transplantation Homologous Immunology and Allergy Enhancer of Zeste Homolog 2 Protein Transplantation business.industry Hematopoietic Stem Cell Transplantation Cell Biology Hematology Vitamin D Deficiency medicine.disease Neoplasm Proteins Cytokine medicine.anatomical_structure Cancer research Molecular Medicine Inhibitor of Differentiation Proteins business CD8 |
| Zdroj: | Transplant Cell Ther |
| ISSN: | 2666-6367 |
| DOI: | 10.1016/j.jtct.2021.09.017 |
| Popis: | 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. © 20XX American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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