TCF-1 controls Treg cell functions that regulate inflammation, CD8+ T cell cytotoxicity and severity of colon cancer.
Nat Immunol
; 22(9): 1152-1162, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34385712
ABSTRACT
The transcription factor TCF-1 is essential for the development and function of regulatory T (Treg) cells; however, its function is poorly understood. Here, we show that TCF-1 primarily suppresses transcription of genes that are co-bound by Foxp3. Single-cell RNA-sequencing analysis identified effector memory T cells and central memory Treg cells with differential expression of Klf2 and memory and activation markers. TCF-1 deficiency did not change the core Treg cell transcriptional signature, but promoted alternative signaling pathways whereby Treg cells became activated and gained gut-homing properties and characteristics of the TH17 subset of helper T cells. TCF-1-deficient Treg cells strongly suppressed T cell proliferation and cytotoxicity, but were compromised in controlling CD4+ T cell polarization and inflammation. In mice with polyposis, Treg cell-specific TCF-1 deficiency promoted tumor growth. Consistently, tumor-infiltrating Treg cells of patients with colorectal cancer showed lower TCF-1 expression and increased TH17 expression signatures compared to adjacent normal tissue and circulating T cells. Thus, Treg cell-specific TCF-1 expression differentially regulates TH17-mediated inflammation and T cell cytotoxicity, and can determine colorectal cancer outcome.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
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Linfocitos T Reguladores
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Neoplasias del Colon
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Factor Nuclear 1-alfa del Hepatocito
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Células Th17
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos