After expression of the αβTCR, induction of the transcription factor RORγt promotes the survival of early CD4+CD8+ double-positive (DP) thymocytes, but its downregulation in late DP cells is required for maturation to the CD4+ or CD8+ single-positive stage. In Nature Communications, Mountz and colleagues show that late-stage DP thymocytes are susceptible to IL-23-induced upregulation of RORγt expression and subsequent apoptosis. IL-23 induced by infection with Aspergillus fumigatus enhances the negative selection of thymocytes but has no effect on positive selection. IL-23 induces expression of the IL-23 receptor on late DP thymocytes but not on early DP thymocytes and acts through the receptor to upregulate RORγt expression and trigger apoptosis. Stimulation via the TCR is required for IL-23-induced apoptosis, which suggests that IL-23 signaling is secondary to an antigen-dependent signal in self-reactive thymocytes. These results correlate with the observation that the thymus becomes much smaller during the infection of mice with A. fumigatus.

Nat. Commun. (8 July 2014) doi:10.1038/ncomms5259