Divergent SATB1 expression across human life span and tissue compartments.
Immunol Cell Biol
; 97(5): 498-511, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30803026
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Gene Expression Regulation
/
Matrix Attachment Region Binding Proteins
Limits:
Adult
/
Aged
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
/
Newborn
Language:
En
Journal:
Immunol Cell Biol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Australia