Divergent SATB1 expression across human life span and tissue compartments
2019
textabstractSpecial 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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