Other
18 Authors
- Nakatsukasa H,
- Chen W,
- Yan X,
- Liu X,
- Wei L,
- Clevers H,
- Qi H,
- Chen X,
- Chen P,
- Chu F,
- Nurieva RI,
- Wang X,
- van der Flier LG,
- Dong C,
- Tian Q,
- Zhong B,
- Neelapu SS,
- Wang A
| First Author | Liu X | Year | 2014 |
| Journal | Nature | Volume | 507 |
| Issue | 7493 | Pages | 513-8 |
| PubMed ID | 24463518 | Mgi Jnum | J:208784 |
| Mgi Id | MGI:5565031 | Doi | 10.1038/nature12910 |
| Citation | Liu X, et al. (2014) Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature 507(7493):513-8 |
| abstractText | In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (TFH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in TFH-cell function, it may not regulate the initial migration of T cells or the induction of the TFH program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation. Here we show that expression of achaete-scute homologue 2 (Ascl2)--a basic helix-loop-helix (bHLH) transcription factor--is selectively upregulated in TFH cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and TFH-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates TFH-related genes whereas it inhibits expression of T-helper cell 1 (TH1) and TH17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4(+) T cells, results in impaired TFH-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances TFH-cell generation. Thus, Ascl2 directly initiates TFH-cell development. |
