Functional definition of a transcription factor hierarchy regulating T cell lineage commitment

T cell factor 1 (Tcf1) is the first T cell-specific protein induced by Notch signaling in the thymus, leading to the activation of two major target genes, Gata3 and Bcl11b. Tcf1 deficiency results in partial arrests in T cell development, high apoptosis, and increased development of B and myeloid cells. Phenotypically, seemingly fully T cell-committed thymocytes with Tcf1 deficiency have promiscuous gene expression and an altered epigenetic profile and can dedifferentiate into more immature thymocytes and non-T cells. Restoring Bcl11b expression in Tcf1-deficient cells rescues T cell development but does not strongly suppress the development of non-T cells; in contrast, expressing Gata3 suppresses their development but does not rescue T cell development. Thus, T cell development is controlled by a minimal transcription factor network involving Notch signaling, Tcf1, and the subsequent division of labor between Bcl11b and Gata3, thereby ensuring a properly regulated T cell gene expression program.Molecular Technology and Informatics for Personalised Medicine and Healt

Canonical Wnt signaling negatively modulates regulatory T cell function

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both invitro and invivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector Tcells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity

Wnt signaling in leukemias and myeloma: T-cell factors are in control

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Discrete roles of canonical and non-canonical Wnt signaling in hematopoiesis and lymphopoiesis

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Multipotent Stromal Cells Induce Human Regulatory T Cells Through a Novel Pathway Involving Skewing of Monocytes Toward Anti-inflammatory Macrophages

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

The Quantity of Autocrine IL-2 Governs the Expansion Potential of CD8(+) T Cells

Tumorimmunolog

Oncologists' practice and attitudes regarding fertility preservation in female cancer patients: a pilot study in the Netherlands

Cervix cance

T Cell Factor 1 Represses CD8(+) Effector T Cell Formation and Function

Stemcel biology/Regenerative medicine (incl. bloodtransfusion