Journal article
Mapping self-associating chromatin hubs identifies Id proteins as key determinants of exhausted CD8 + T cell fate
Nature immunology
07/06/2026
DOI: 10.1038/s41590-026-02578-4
PMID: 42409948
Abstract
Within days of exposure to chronic viral infections, activated CD8
T cells differentiate into Tcf1
Slamf6
Tim3
exhaustion-prone effector T (T
) cells or self-renewing Tcf1
Slamf6
Tim3
precursor exhausted T (T
) cells. Here we showed that early CD8
T
cell fates were imprinted by forming subset-specific, self-associating chromatin hubs. Chromatin hub assembly coincided with effector or stemness gene induction and identified the transcription cofactors Id2 and Id3 as key regulators that promoted CD8
T
and CD8
T
cell fates, respectively. Id2 drove CD8
T
cell specification by activating effector genes, while suppressing genes involved in exhaustion and stemness. In contrast, Id3-repressed effector genes but upregulated IL-7Rα and AhR, thereby maintaining the CD8
T
cell pool. Mechanistically, Id2 and Id3 exhibited a distinct impact on the chromatin accessibility landscape in early CD8
T
cells by engaging Runx3 and Tcf1 transcription factors along with E proteins. These findings indicated that reshaping chromatin architecture represents a critical means for specifying CD8
T
cell fates and ensuring lineage stability.
Details
- Title: Subtitle
- Mapping self-associating chromatin hubs identifies Id proteins as key determinants of exhausted CD8 + T cell fate
- Creators
- Wei Hu - Hackensack University Medical CenterQing Chen - George Washington UniversityShaoqi Zhu - George Washington UniversityShengen Shawn Hu - University of VirginiaHaibo Yu - Hackensack University Medical CenterVanita Patel - Hackensack University Medical CenterYing Wang - Hackensack University Medical CenterVladimir P Badovinac - University of IowaYi Zhang - Hackensack University Medical CenterChongzhi Zang - University of VirginiaWeiqun Peng - George Washington UniversityHai-Hui Xue - New Jersey Veterans Affairs Health Care System, East Orange, NJ, USA. haihui.xue@hmh-cdi.org
- Resource Type
- Journal article
- Publication Details
- Nature immunology
- DOI
- 10.1038/s41590-026-02578-4
- PMID
- 42409948
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Publisher
- Springer Nature
- Grant note
- CA290808 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) AI191414 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI112579 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI139874 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI187349 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) BX005771 / U.S. Department of Veterans Affairs (Department of Veterans Affairs) AI121080 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI114543 / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
- Language
- English
- Electronic publication date
- 07/06/2026
- Academic Unit
- Pathology
- Record Identifier
- 9985180788002771
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