|
| Status |
Public on Jan 01, 2014 |
| Title |
Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development [array] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| |
|
| Overall design |
Decide gene expression patterns of CD4+ T cells with overexpressed Ascl2 or Tfh cells
|
| |
|
| Contributor(s) |
Liu X, Yan X, Wei L, Dong C |
| Citation(s) |
24463518 |
| |
| Submission date |
Nov 29, 2013 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Lai Wei |
| E-mail(s) |
[email protected]
|
| Phone |
3014961480
|
| Organization name |
NIH/NEI/NCCAM
|
| Street address |
10 Center Dr. Room 2B47
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (7)
|
| GSM1276930 |
empty vector transfected CD4+ T cells, biological rep1 |
| GSM1276931 |
empty vector transfected CD4+ T cells, biological rep2 |
| GSM1276932 |
Ascl2 vector transfected CD4+ T cells, biological rep1 |
|
| This SubSeries is part of SuperSeries: |
| GSE52840 |
Transcription factor Achaete-Scute homologue 2 initiates T follicular helper cell development |
|
| Relations |
| BioProject |
PRJNA230275 |
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