期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 97, 期 5, 页码 498-511出版社
WILEY
DOI: 10.1111/imcb.12233
关键词
Human CD8(+) T cells; PD-1; SATB1
资金
- Melbourne International Research Scholarship (MIRS)
- Melbourne International Fee Remission Scholarship (MIFRS)
- Australian National Health and Medical Research Council (NHMRC) [1071916, 1113293]
- NHMRC [1160333, 1117766]
- JDRF Career Development Award [5C-DA2014210-A-N]
- Department of Obstetrics and Gynaecology from the University of Melbourne
- University of Melbourne
- National Health and Medical Research Council of Australia [1160333, 1117766] Funding Source: NHMRC
Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8(+) T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
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