Divergent SATB1 expression across human life span and tissue compartments

Simone Nüssing, Hui Fern Koay, Sneha Sant, Thomas Loudovaris, Stuart I. Mannering, Martha Lappas, Yves d′Udekem, Igor E. Konstantinov, Stuart P. Berzins, Guus F. Rimmelzwaan, Stephen J Turner, E. Bridie Clemens, Dale I. Godfrey, Thi H.O. Nguyen, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Number of pages14
JournalImmunology and Cell Biology
DOIs
Publication statusAccepted/In press - 25 Feb 2019

Keywords

  • Human CD8 T cells
  • PD-1
  • SATB1

Cite this

Nüssing, S., Koay, H. F., Sant, S., Loudovaris, T., Mannering, S. I., Lappas, M., ... Kedzierska, K. (Accepted/In press). Divergent SATB1 expression across human life span and tissue compartments. Immunology and Cell Biology. https://doi.org/10.1111/imcb.12233
Nüssing, Simone ; Koay, Hui Fern ; Sant, Sneha ; Loudovaris, Thomas ; Mannering, Stuart I. ; Lappas, Martha ; d′Udekem, Yves ; Konstantinov, Igor E. ; Berzins, Stuart P. ; Rimmelzwaan, Guus F. ; Turner, Stephen J ; Clemens, E. Bridie ; Godfrey, Dale I. ; Nguyen, Thi H.O. ; Kedzierska, Katherine. / Divergent SATB1 expression across human life span and tissue compartments. In: Immunology and Cell Biology. 2019.
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title = "Divergent SATB1 expression across human life span and tissue compartments",
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.",
keywords = "Human CD8 T cells, PD-1, SATB1",
author = "Simone N{\"u}ssing and Koay, {Hui Fern} and Sneha Sant and Thomas Loudovaris and Mannering, {Stuart I.} and Martha Lappas and Yves d′Udekem and Konstantinov, {Igor E.} and Berzins, {Stuart P.} and Rimmelzwaan, {Guus F.} and Turner, {Stephen J} and Clemens, {E. Bridie} and Godfrey, {Dale I.} and Nguyen, {Thi H.O.} and Katherine Kedzierska",
year = "2019",
month = "2",
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Nüssing, S, Koay, HF, Sant, S, Loudovaris, T, Mannering, SI, Lappas, M, d′Udekem, Y, Konstantinov, IE, Berzins, SP, Rimmelzwaan, GF, Turner, SJ, Clemens, EB, Godfrey, DI, Nguyen, THO & Kedzierska, K 2019, 'Divergent SATB1 expression across human life span and tissue compartments' Immunology and Cell Biology. https://doi.org/10.1111/imcb.12233

Divergent SATB1 expression across human life span and tissue compartments. / Nüssing, Simone; Koay, Hui Fern; Sant, Sneha; Loudovaris, Thomas; Mannering, Stuart I.; Lappas, Martha; d′Udekem, Yves; Konstantinov, Igor E.; Berzins, Stuart P.; Rimmelzwaan, Guus F.; Turner, Stephen J; Clemens, E. Bridie; Godfrey, Dale I.; Nguyen, Thi H.O.; Kedzierska, Katherine.

In: Immunology and Cell Biology, 25.02.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Divergent SATB1 expression across human life span and tissue compartments

AU - Nüssing, Simone

AU - Koay, Hui Fern

AU - Sant, Sneha

AU - Loudovaris, Thomas

AU - Mannering, Stuart I.

AU - Lappas, Martha

AU - d′Udekem, Yves

AU - Konstantinov, Igor E.

AU - Berzins, Stuart P.

AU - Rimmelzwaan, Guus F.

AU - Turner, Stephen J

AU - Clemens, E. Bridie

AU - Godfrey, Dale I.

AU - Nguyen, Thi H.O.

AU - Kedzierska, Katherine

PY - 2019/2/25

Y1 - 2019/2/25

N2 - 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.

AB - 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.

KW - Human CD8 T cells

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Nüssing S, Koay HF, Sant S, Loudovaris T, Mannering SI, Lappas M et al. Divergent SATB1 expression across human life span and tissue compartments. Immunology and Cell Biology. 2019 Feb 25. https://doi.org/10.1111/imcb.12233