Divergent SATB1 expression across human life span and tissue compartments

• DOI: 10.1111/imcb.12233
• Publication Date: 2019-02-26T06:17:55Z
• Authors: 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 HO Nguyen; Katherine Kedzierska
• Keywords: Adult; Male; 0301 basic medicine; Aging; Thymocytes; EMC OR-01; Programmed Cell Death 1 Receptor; Infant, Newborn; 610; 500; Infant; Original Articles; Matrix Attachment Region Binding Proteins; CD8-Positive T-Lymphocytes; Middle Aged; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Organ Specificity; Child, Preschool; Humans; Female; Aged

AbstractSpecial 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.