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IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection
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IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection
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Journal Article
IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection
2015
Overview
IL-7 is known to control the survival of immature DN thymocytes before β-selection. Guidos and colleagues show that during β-selection, IL-7 controls the growth and differentiation of thymocytes, in part by repressing the transcription factor Bcl-6.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 13/95
/ 38/61
/ 38/77
/ 64/60
/ 82/80
/ 96/21
/ Animals
/ Mice
/ Proto-Oncogene Proteins c-bcl-2 - genetics
/ Proto-Oncogene Proteins c-bcl-2 - immunology
/ Proto-Oncogene Proteins c-bcl-6 - deficiency
/ Proto-Oncogene Proteins c-bcl-6 - genetics
/ Proto-Oncogene Proteins c-bcl-6 - immunology
/ Receptor, Notch1 - immunology
/ Receptors, Antigen, T-Cell, alpha-beta - genetics
/ Receptors, Antigen, T-Cell, alpha-beta - immunology
/ T cells
