Project description:In thymus hematopoietic precursor cells differentiate into αβ T cells, γδ T cells, mucosa-associated invariant T cells (MAIT), and natural killer T (NKT) cells. We show that both ablation of NFATc1 or its induction during the DN stages of thymocyte development leads to an almost normal thymocyte development but a marked increase in γδ T cells. The γδ cells deficient for NFATc1 acquire an NKT γδ cell phenotype that exhibits the expression of CD4 co-receptor, the NK1.1 marker, the augmented usage of the Vγ1.1 and Vδ6.3 segments, and an increased in IL4 and IFN-γ production.
Project description:In thymus hematopoietic precursor cells differentiate into αβ T cells, γδ T cells, mucosa-associated invariant T cells (MAIT), and natural killer T (NKT) cells. We show that both ablation of NFATc1 or its induction during the DN stages of thymocyte development leads to an almost normal thymocyte development but a marked increase in γδ T cells. The γδ cells deficient for NFATc1 acquire an NKT γδ cell phenotype that exhibits the expression of CD4 co-receptor, the NK1.1 marker, the augmented usage of the Vγ1.1 and Vδ6.3 segments, and an increased in IL4 and IFN-γ production.
Project description:In thymus hematopoietic precursor cells differentiate into αβ T cells, γδ T cells, mucosa-associated invariant T cells (MAIT), and natural killer T (NKT) cells. We show that both ablation of NFATc1 or its induction during the DN stages of thymocyte development leads to an almost normal thymocyte development but a marked increase in γδ T cells. The γδ cells deficient for NFATc1 acquire an NKT γδ cell phenotype that exhibits the expression of CD4 co-receptor, the NK1.1 marker, the augmented usage of the Vγ1.1 and Vδ6.3 segments, and an increased in IL4 and IFN-γ production.
Project description:NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are unknown. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibited only P2 promoter-derived Nfatc1b expression, preTCR-positive thymocytes expressed both Nfatc1b and P1 promoter-derived Nfatc1a transcripts. Inducing NFATc1a activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1a from P2 promoter impaired thymocyte development resulting in severe T cell lymphopenia. Additionally, we show that NFATc1 activity suppressed the B-lineage potential of immature thymocytes, and consolidated their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity was vital in facilitating T cell differentiation and to prevent T-acute lymphoblastic leukemia (T-ALL) development. Altogether, our results show NFATc1 activity is crucial in determining the T cell fate of thymocytes.
Project description:Cytotoxic T Lymphocytes (CTLs) are effector CD8+T cells that eradicate infected and malignant cells from organism. We analyze the role of the transcription factor NFATc1 in activation and cytotoxicity of murine CD8+ T lymphocytes
Project description:Cytotoxic T Lymphocytes (CTLs) are effector CD8+T cells that eradicate infected and malignant cells from organism. We analyze the role of the transcription factor NFATc1 in activation and cytotoxicity of murine CD8+ T lymphocytes