E-GEOD-52838 - Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development [array]

Status
Released on 1 January 2014, last updated on 13 January 2014
Organism
Mus musculus
Samples (7)
Array (1)
Protocols (7)
Description
In immune responses, activated T cells migrate to B cell follicles and develop to T follicular helper (Tfh) cells, a new subset of CD4+ T cells specialized in providing help to B lymphocytes in the induction of germinal centers 1-3. Although Bcl6 has been shown to be essential in Tfh cell function, it may not regulate the initial migration of T cells 4 or the induction of Tfh program as exampled by CXCR5 upregulation 5. Here, we show that the Achaete-Scute homologue 2 (Ascl2) gene that encodes a basic helix-loop-helix (bHLH) transcription factor 6, is selectively upregulated in its expression in Tfh cells. Ectopic expression of Ascl2 uniquely upregulates CXCR5 but not Bcl6 and downregulates CCR7 expression in T cells in vitro and accelerates T cell migration to the follicles and Tfh cell development in vivo. Combined transcriptome profiling and genome-wide occupancy analysis indicate that Ascl2 directly regulates Tfh-related genes while inhibits expression of Th1 and Th17 genes. Acute deletion of Ascl2 as well as blockade of its function with the Id3 protein in peripheral CD4+ T cells results in a failure in Tfh cell development and the germinal center response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances Tfh cell generation. Thus, Ascl2 critically and directly initiates Tfh cell development. Decide gene expression patterns of CD4+ T cells with overexpressed Ascl2 or Tfh cells
Experiment type
transcription profiling by array 
Contacts
Chen Dong, Lai Wei, Xiaowei Yan, Xindong Liu
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-52838.idf.txt
Sample and data relationshipE-GEOD-52838.sdrf.txt
Raw data (1)E-GEOD-52838.raw.1.zip
Processed data (1)E-GEOD-52838.processed.1.zip
Array designA-AFFY-130.adf.txt
Links