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@ARTICLE{Heyden:282555,
author = {Heyden, Leonie and Rausch, Lisa and Shannon, Michael H and
Dryburgh, Lachlan and Moreira, Marcela L and Frolov, Aleksej
and Scheffler, Christina M and van Elsas, Marit J and Tong,
Junming and Hidajat, Olivia and Wijesinghe, Sharanya K M and
Li, Sining and Horvatic, Helena and Huynh-Anh, Nhat Truong
and Gago da Graça, Catarina and Tsui, Carlson and Köhne,
Maren and Sommer, Daniel and Wunderlich, F Thomas and von
Scheidt, Bianca and Park, Simone L and Mackay, Laura K and
Utzschneider, Daniel T and Schröder, Jan and Turner,
Stephen J and Darcy, Phillip K and Beyer, Marc D and
Abdullah, Zeinab and Kallies, Axel},
title = {{T}ranscriptional regulator {SATB}1 limits {CD}8+ {T} cell
population expansion and effector differentiation in chronic
infection and cancer.},
journal = {Nature immunology},
volume = {26},
number = {12},
issn = {1529-2908},
address = {London},
publisher = {Springer Nature Limited},
reportid = {DZNE-2025-01318},
pages = {2312 - 2327},
year = {2025},
abstract = {CD8+ T cells are major mediators of antiviral and antitumor
immunity. During persistent antigen stimulation as in
chronic infection and cancer, however, they differentiate
into exhausted T cells that display impaired functionality.
Precursors of exhausted T (TPEX) cells exhibit stem-like
properties, including high proliferative, self-renewal and
developmental potential, and are responsible for long-term
CD8+ T cell responses against persistent antigens. Here we
identify the chromatin organizer and transcriptional
regulator SATB1 as a major regulator of exhausted CD8+ T
cell differentiation. SATB1 was specifically expressed in
TPEX cells where it limited population expansion and
effector differentiation while preserving functionality of
CD8+ T cells. SATB1 downregulation was required for TPEX
cell-to-effector cell differentiation in chronic infection
and contributed to coordinated effector and memory
differentiation in acute viral infection. DNA binding of
SATB1 regulated gene expression both dependent and
independent of chromatin accessibility. Finally, SATB1
limited antitumor CD8+ and chimeric antigen receptor T cell
immunity. Overall, our results identify SATB1 as a central
regulator of precursor fate and effector differentiation of
CD8+ T cells both in infection and in cancer.},
keywords = {Matrix Attachment Region Binding Proteins: metabolism /
Matrix Attachment Region Binding Proteins: genetics / Matrix
Attachment Region Binding Proteins: immunology /
CD8-Positive T-Lymphocytes: immunology / Animals / Cell
Differentiation: immunology / Mice / Immunologic Memory /
Mice, Inbred C57BL / Neoplasms: immunology / Humans /
Persistent Infection: immunology / Lymphocytic
Choriomeningitis: immunology / Mice, Knockout / Cell
Proliferation / Lymphocytic choriomeningitis virus:
immunology / Matrix Attachment Region Binding Proteins (NLM
Chemicals) / Satb1 protein, mouse (NLM Chemicals) / SATB1
protein, human (NLM Chemicals)},
cin = {AG Beyer / AG Schultze / PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013035 / I:(DE-2719)1013038 /
I:(DE-2719)1013031},
pnm = {351 - Brain Function (POF4-351) / 354 - Disease Prevention
and Healthy Aging (POF4-354) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-354 /
G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41145844},
doi = {10.1038/s41590-025-02316-2},
url = {https://pub.dzne.de/record/282555},
}