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

ABSTRACT: Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (?-selection) of TCR?(+) 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 ?-chain (Tcra). Interleukin 7 (IL-7) promotes the survival of TCR?(-) DN thymocytes by inducing expression of the pro-survival molecule Bcl-2, but the functions of IL-7 during ?-selection have remained unclear. Here we found that IL-7 signaled TCR?(+) 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 ?-selection.

SUBMITTER: Boudil A 

PROVIDER: S-EPMC4368453 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature