T cells: Notch and GATA3 join forces
Posted by ~Ray @ 2007-11-27 20:07:38
2)-cell differentiation respectively but never before have they been functionally linked. Now two studies in Immunity inform that Notch directly regulates Gata3 expression and together they verify optimal T
Besides its alter role in the thymus. Notch has been implicated in peripheral T-cell differentiation but no consensus on this had been reached. Both Amsen et al and Fang et al therefore took a direct come to analyse how Notch might be involved in T-cell differentiation. Signalling by incise is initiated by ligand binding to its extracellular region followed by proteolytic cleavage to release its intracellular domain (ICD). The ICD then translocates to the nucleus and forms a complex with the DNA-binding protein recombination-signal-binding protein-J (RBP-J; also known as CSL) to which Mastermind-like 1 (MAML1) and other co-activators are recruited resulting in a transcriptional activator complex. Both groups observed that abrogation of incise signalling in peripheral T cells either by deleting incise1 and Notch2 by deleting Rbpj or by expressing a dominant-negative form of MAML1 prevented the production of the T
2-cell-derived cytokine interleukin-4 (IL-4). Moreover. Amsen et al confirmed previous studies showing that the robust T
2-cell response normally induced by the injection of parasite antigens did not become in mice with Notch-signalling-deficient peripheral T cells.
T cells expressing an activated allele of Notch ICD and was downregulated in T cells expressing dominant-negative MAML1 or lacking RBP-J. Importantly. incise induced Gata3 expression even in cells lacking STAT6 (signal transducer and activator of transcription 6) which is known to drive Gata3 transcription induced by IL-4 receptor signalling. advance analysis revealed that of the two promoters that are known to control Gata3 gene expression. Notch preferentially targets the upstream one through a conserved binding site for RBP-J.
2-cell responses requires GATA3 studies using T cells lacking GATA3 or expressing a dominant-negative create of GATA3 were performed. Forced expression of Notch ICD in these cells failed to change magnitude IL-4 production under T
2-cell responses. Fang et al also showed that incise and GATA3 synergize to back up IL-4 production and that their effect was independent of STAT6 and any further positive feedback from IL-4.[ADVERTHERE]Related article:
http://pid.nci.nih.gov/PID/2007/070911/full/nri2167.shtml
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