TCF-1 controls Treg functions that regulate inflammation, CD8 T-cell cytotoxicity, and severity of colon cancer
نویسندگان
چکیده
Abstract The transcription factor TCF-1 is essential for the development and function of T regulatory (Treg) cells, however its poorly understood. Here, we show that primarily suppresses genes are co-bound by Foxp3. Single-cell RNA-seq analysis identified effector- central-memory Treg-cells with differential expression Klf2 memory activation markers. deficiency did not change core Treg transcriptional signature, but promoted alternative signaling pathways whereby became activated gained gut-homing TH17 characteristics. TCF-1-deficient strongly suppressed T-cell proliferation cytotoxicity, were compromised in controlling CD4+ polarization inflammation. In mice polyposis, cell-specific tumor growth. Consistently, tumor-infiltrating cells colorectal cancer patients showed lower increased signatures compared to adjacent normal tissue circulating T-cells. Thus, differentially regulates TH17-mediated inflammation can determine outcome. Supported NIH R01 AI 108682 (FG & KK), RO1 147652 (FG), R35GM138283 (MK), Praespero Innovation Award Alberta, Canada KK)
منابع مشابه
AMPKα1: A glucose sensor that controls CD8 T-cell memory
The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quies...
متن کاملNotch controls effector CD8+ T cell differentiation
CD8+ T cell recognition of foreign antigen induces the expansion of the few T cells bearing an appropriate T cell receptor and the acquisition of effector functions. These effector CD8+ T (Te) cells eliminate the pathogen by secretion of cytokines or by direct cytotoxicity. Following this initial clonal expansion, 90-95% of the Te cells die while the few others further differentiate into memory...
متن کاملCD8 controls T cell cross-reactivity.
Estimates of human αβ TCR diversity suggest that there are <10(8) different Ag receptors in the naive T cell pool, a number that is dwarfed by the potential number of different antigenic peptide-MHC (pMHC) molecules that could be encountered. Consequently, an extremely high degree of cross-reactivity is essential for effective T cell immunity. Ag recognition by T cells is unique in that it invo...
متن کاملCharacterization of human T cells that regulate neutrophilic skin inflammation.
It is unknown whether neutrophilic inflammations can be regulated by T cells. This question was analyzed by studying acute generalized exanthematous pustulosis (AGEP), which is a severe drug hypersensitivity resulting in intraepidermal or subcorneal sterile pustules. Recently, we found that drug-specific blood and skin T cells from AGEP patients secrete high levels of the potent neutrophil-attr...
متن کاملColitis immunoregulation by CD8+ T cell requires T cell cytotoxicity and B cell peptide antigen presentation.
Deficient immunoregulation by CD4+ T cells is an important susceptibility trait for inflammatory bowel disease, but the role of other regulatory cell types is less understood. This study addresses the role and mechanistic interaction of B cells and CD8+ T cells in controlling immune-mediated colitis. The genetic requirements for B cells and CD8+ T cells to confer protective immunoregulation wer...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2022
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.208.supp.119.16