IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Boudil, A; Matei, IR; Shih, HY; Bogdanoski, G; Yuan, JS; Chang, SG; Montpellier, B; Kowalski, PE; Voisin, V; Bashir, S; Bader, GD; Krangel, MS; Guidos, CJ

Published Date

  • March 19, 2015

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 397 - 405

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.3122

Citation Source

  • Scopus