TY  - JOUR
AU  - Man, Kevin
AU  - Duarte da Silva, Vinicius A
AU  - Potemkin, Nikita
AU  - Gabriel, Sarah S
AU  - Mason, Teisha
AU  - Elmzzahi, Tarek
AU  - De Lima Moreira, Marcela
AU  - Su, Chun-Hsi
AU  - Mackay, Laura
AU  - Beyer, Marc D
AU  - Schröder, Jan
AU  - Gasteiger, Georg
AU  - Kallies, Axel
TI  - Stem-like tissue-resident memory T cells control functional heterogeneity and reactivation of T cell memory in the intestine.
JO  - Science immunology
VL  - 10
IS  - 112
SN  - 2470-9468
CY  - Washington, DC
PB  - AAAS
M1  - DZNE-2025-01221
SP  - eadw1992
PY  - 2025
AB  - Tissue-resident memory T (TRM) cells provide localized immunity against intracellular pathogens and cancer. Upon antigen reencounter, TRM cells differentiate into effector cells while also giving rise to another generation of memory cells. Here, we show that intestinal TRM cells that express the transcriptional regulators TCF1 or ID3 exhibit stem-like memory properties and are endowed with a superior capacity to regenerate effector and memory T cells after pathogen reencounter. Ablation of TCF1 using a TRM cell-specific mouse model resulted in impaired formation of intestinal TRM cells, altered their transcriptional heterogeneity, and increased their differentiation into tissue-confined and recirculating CX3CR1+ effector cells during recall. TGF-β and retinoic acid were required for formation and survival of TCF1- and ID3-expressing TRM cells and restrained their differentiation into CX3CR1+ effector cells during reinfection. Thus, stem-like cells control the quality and recall capacity of TRM cells, thereby contributing to anamnestic memory responses.
KW  - Animals
KW  - Immunologic Memory: immunology
KW  - Memory T Cells: immunology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Intestines: immunology
KW  - Hepatocyte Nuclear Factor 1-alpha: genetics
KW  - Hepatocyte Nuclear Factor 1-alpha: immunology
KW  - Cell Differentiation: immunology
KW  - Inhibitor of Differentiation Proteins: immunology
KW  - Inhibitor of Differentiation Proteins: genetics
KW  - CX3C Chemokine Receptor 1
KW  - Stem Cells: immunology
KW  - Mice, Knockout
KW  - T Cell Transcription Factor 1: genetics
KW  - T Cell Transcription Factor 1: immunology
KW  - Hepatocyte Nuclear Factor 1-alpha (NLM Chemicals)
KW  - Hnf1a protein, mouse (NLM Chemicals)
KW  - Idb3 protein, mouse (NLM Chemicals)
KW  - Inhibitor of Differentiation Proteins (NLM Chemicals)
KW  - CX3C Chemokine Receptor 1 (NLM Chemicals)
KW  - T Cell Transcription Factor 1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41171881
DO  - DOI:10.1126/sciimmunol.adw1992
UR  - https://pub.dzne.de/record/281842
ER  -