| Autor: |
Boudil, Amine, Matei, Irina R, Shih, Han-Yu, Bogdanoski, Goce, Yuan, Julie S, Chang, Stephen G, Montpellier, Bertrand, Kowalski, Paul E, Voisin, Veronique, Bashir, Shaheena, Bader, Gary D, Krangel, Michael S, Guidos, Cynthia J |
| Předmět: |
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| Zdroj: |
Nature Immunology; Apr2015, Vol. 16 Issue 4, p397-405, 9p, 8 Graphs |
| Abstrakt: |
Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (β-selection) of TCRβ+ 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 α-chain (Tcra). Interleukin 7 (IL-7) promotes the survival of TCRβ− DN thymocytes by inducing expression of the pro-survival molecule Bcl-2, but the functions of IL-7 during β-selection have remained unclear. Here we found that IL-7 signaled TCRβ+ 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 β-selection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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