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During development in the thymus, invariant natural killer T (iNKT) cells commit to one of three major functionally different subsets, iNKT1, iNKT2, and iNKT17. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets, with strong signaling promoting iNKT2 and iNKT17 development. Altering TCR diversity or signaling diminishes iNKT2 and iNKT17 cell subset development in a cell-intrinsic manner. Decreased TCR signaling affects the persistence of Egr2 expression and the upregulation of PLZF. By genome-wide comparison of chromatin accessibility, we identify a subset of iNKT2-specific regulatory elements containing NFAT and Egr binding motifs that is less accessible in iNKT2 cells that develop from reduced TCR signaling. These data suggest that variable TCR signaling modulates regulatory element activity at NFAT and Egr binding sites exerting a determinative influence on the dynamics of gene enhancer accessibility and the developmental fate of iNKT cells.
This article was published in the following journal.
Name: Nature communications
Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show t...
Due to their immunoregulatory properties, several specialized cell subsets, including regulatory T (Treg), invariant natural killer T (iNKT) and regulatory B (Breg) cells, are involved in the pathogen...
Innate T cells, NK cells, and innate-like lymphocytes (ILCs) share transcriptional signatures that translate into overlapping developmental and functional programs. A prominent example for genes that ...
During the last years, intensive research has shed light in the transcriptional networks that shape the invariant NKT (iNKT) cell lineage and guide the choices towards functionally distinct iNKT cell ...
Invariant natural killer T cells (iNKTs) are distinct from conventional T cells. iNKT cells express a semi-invariant T cell receptor (TCR) that can specifically recognize lipid antigens presented by C...
Invariant Natural killer T (iNKT) cells are a unique subset of lymphocytes that express homogeneous TCR recognizing KRN7000 which was up-regulated by many kinds of cancer cells. PD-1+CD8+T...
Stem cells can develop into every cell, every tissue and every organ in the human body, e.g., they can make any kind of cells in the human body. Stem cells reproduce themselves many times...
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Invariant Natural killer T (iNKT) cells are a unique subset of lymphocytes that express homogeneous TCR recognizing KRN7000 which was up-regulated by many kinds of cancer cells.The hypothe...
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Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.
A thymus-dependent nonapeptide found in normal blood. Stimulates the formation of E rosettes and is believed to be involved in T-cell differentiation.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activa
A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)
A myogenic regulatory factor that controls myogenesis. Myogenin is induced during differentiation of every skeletal muscle cell line that has been investigated, in contrast to the other myogenic regulatory factors that only appear in certain cell types.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...