| First Author | Boudil A | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 4 | Pages | 397-405 |
| PubMed ID | 25729925 | Mgi Jnum | J:231646 |
| Mgi Id | MGI:5771979 | Doi | 10.1038/ni.3122 |
| Citation | Boudil A, et al. (2015) IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte beta-selection. Nat Immunol 16(4):397-405 |
| abstractText | Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (beta-selection) of TCRbeta(+) CD4(-)CD8(-) double-negative stage 3 (DN3) and DN4 progenitor cells that differentiate into CD4(+)CD8(+) double-positive (DP) thymocytes, which then rearrange the locus encoding the TCR alpha-chain (Tcra). Interleukin 7 (IL-7) promotes the survival of TCRbeta(-) DN thymocytes by inducing expression of the pro-survival molecule Bcl-2, but the functions of IL-7 during beta-selection have remained unclear. Here we found that IL-7 signaled TCRbeta(+) DN3 and DN4 thymocytes to upregulate genes encoding molecules involved in cell growth and repressed the gene encoding the transcriptional repressor Bcl-6. Accordingly, IL-7-deficient DN4 cells lacked trophic receptors and did not proliferate but rearranged Tcra prematurely and differentiated rapidly. Deletion of Bcl6 partially restored the self-renewal of DN4 cells in the absence of IL-7, but overexpression of BCL2 did not. Thus, IL-7 critically acts cooperatively with signaling via the pre-TCR and Notch1 to coordinate proliferation, differentiation and Tcra recombination during beta-selection. |
