- Title
- Divergent SATB1 expression across human life span and tissue compartments
- Creator
- Nüssing, Simone; Koay, Hui-Fern; Sant, Sneha; Loudovaris, Thomas; Mannering, Stuart; Lappas, Martha; d′Udekem, Yves; Konstantinov, Igor; Berzins, Stuart; Rimmelzwaan, Guus; Turner, Stephen; Clemens, Bridie; Godfrey, Dale; Nguyen, Thi; Kedzierska, Katherine
- Date
- 2019
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/168419
- Identifier
- vital:13864
- Identifier
-
https://doi.org/10.1111/imcb.12233
- Identifier
- ISBN:0818-9641
- Abstract
- 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.
- Publisher
- John Wiley and Sons Inc.
- Relation
- Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © 2019 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- 0601 Biochemistry and Cell Biology; 1107 Immunology; Human CD8 + T cells; PD-1; SATB1
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