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Nat Commun 2021 02 26;12(1):1333. Epub 2021 Feb 26.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

T follicular helper (T) cells are specialized effector CD4 T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in T cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N-methyladenosine (mA) modification) in CD4 T cells impairs T differentiation and germinal center responses in a cell-intrinsic manner in mice. Read More

Cell Mol Immunol 2021 Mar 31;18(3):644-659. Epub 2020 Aug 31.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road 2, 100193, Beijing, China.

Tcf-1 (encoded by Tcf7) not only plays critical roles in promoting T cell development and differentiation but also has been identified as a tumor suppressor involved in preventing T cell malignancy. However, the comprehensive mechanisms of Tcf-1 involved in T cell transformation remain poorly understood. In this study, Tcf7 mice were crossed with Vav-cre, Lck-cre, or Cd4-cre mice to delete Tcf-1 conditionally at the beginning of the HSC, DN2-DN3, or DP stage, respectively. Read More

Front Immunol 2020 20;11:470. Epub 2020 Mar 20.

T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States.

The transcription factor TCF-1 (encoded by ) plays critical roles in several lineages of hematopoietic cells. In this study, we examined the molecular basis for regulation in T cells, innate lymphoid cells, and migratory conventional dendritic cells that we find express . We identified a 1 kb regulatory element crucial for the initiation of expression in T cells and innate lymphoid cells, but dispensable for expression in -expressing dendritic cells. Read More

Cancer Immunol Res 2020 03 17;8(3):309-320. Epub 2020 Jan 17.

Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)-expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function and can improve the antitumor properties of T cells. Read More

Trends Immunol 2019 12 14;40(12):1149-1162. Epub 2019 Nov 14.

School of Cancer Medicine, LaTrobe University, Heidelberg, VIC 3084, Australia; Cancer Immunobiology Program, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Molecular Sciences, College of Science, Health and Engineering, LaTrobe University, Bundoora, VIC 3083, Australia. Electronic address:

T cell factor-1 (TCF-1), encoded by Tcf7, is a transcription factor and histone deacetylase (HDAC) essential for commitment to both the T cell and the innate lymphoid cell (ILC) lineages in mammals. In this review, we discuss the multifunctional role of TCF-1 in establishing these lineages and the requirement for TCF-1 throughout lineage differentiation and maintenance of lineage stability. We highlight recent reports showing promise for TCF-1 as a novel biomarker to identify recently characterized subsets of exhausted CD8 T cells that may help to predict patient responses to immune checkpoint blockade (ICB). Read More

Front Immunol 2018 7;9:964. Epub 2018 May 7.

Molecular Immunogenetics Group, Genetics, Ribeirão Preto Medical School, Universidade de São Paulo, São Paulo, Brazil.

The function of medullary thymic epithelial cells (mTECs) is associated with thymocyte adhesion, which is crucial for the negative selection of autoreactive thymocytes in the thymus. This process represents the root of central tolerance of self-components and prevents the onset of autoimmune diseases. Since thymic epithelia correspond to an important target of donor T cells during the onset of chronic graft-vs-host-disease, mTEC-thymocyte adhesion may have implications for alloimmunity. Read More

Nat Med 2016 Jan 7;22(1):84-90. Epub 2015 Dec 7.

Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada.

The glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor transduce nutrient-stimulated signals to control beta cell function. Although the GLP-1 receptor (GLP-1R) is a validated drug target for diabetes, the importance of the GIP receptor (GIPR) for the function of beta cells remains uncertain. We demonstrate that mice with selective ablation of GIPR in beta cells (MIP-Cre:Gipr(Flox/Flox); Gipr(-/-βCell)) exhibit lower levels of meal-stimulated insulin secretion, decreased expansion of adipose tissue mass and preservation of insulin sensitivity when compared to MIP-Cre controls. Read More

Annu Rev Immunol 2015 4;33:607-42. Epub 2015 Feb 4.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.

The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the transcriptome level and express many elements of the core T cell transcriptional program, including Notch, Gata3, Tcf7, and Bcl11b. Read More

PLoS One 2014 23;9(12):e115803. Epub 2014 Dec 23.

Immune Cells and Inflammation Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, United States of America.

Natural killer T (NKT) cells are a component of innate and adaptive immune systems implicated in immune, autoimmune responses and in the control of obesity and cancer. NKT cells develop from common CD4+ CD8+ double positive (DP) thymocyte precursors after the rearrangement and expression of T cell receptor (TCR) Vα14-Jα18 gene. Temporal regulation and late appearance of Vα14-Jα18 rearrangement in immature DP thymocytes has been demonstrated. Read More

J Immunol 2013 Oct 13;191(8):4383-91. Epub 2013 Sep 13.

Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia;

Innate lymphocyte populations play a central role in conferring protective immunity at the mucosal frontier. In this study, we demonstrate that T cell factor 1 (TCF-1; encoded by Tcf7), a transcription factor also important for NK and T cell differentiation, is expressed by multiple innate lymphoid cell (ILC) subsets, including GATA3(+) nuocytes (ILC2) and NKp46(+) ILCs (ILC3), which confer protection against lung and intestinal inflammation. TCF-1 was intrinsically required for the differentiation of both ILC2 and NKp46(+) ILC3. Read More

Nat Genet 1998 Aug;19(4):379-83

Department of Immunology, University Hospital, Utrecht, The Netherlands.

Mutations of the genes encoding APC or beta-catenin in colon carcinoma induce the constitutive formation of nuclear beta-catenin/Tcf-4 complexes, resulting in activated transcription of Tcf target genes. To study the physiological role of Tcf-4 (which is encoded by the Tcf7/2 gene), we disrupted Tcf7/2 by homologous recombination. Tcf7/2-/- mice die shortly after birth. Read More

J Biol Chem 1992 Apr;267(12):8530-6

Department of Clinical Immunology, University Hospital Utrecht, The Netherlands.

We have recently isolated cDNA clones representing four alternative splice forms of a T cell-specific transcription factor, TCF-1. Here we report the characterization of the human gene encoding this factor. The TCF-1 gene is contained in 10 exons including an untranslated first exon. Read More