The microRNA biogenesis machinery modulates lineage commitment during αβ T cell development.

ABSTRACT: Differentiation of CD4(+) helper and CD8(+) cytotoxic αβ T cells from CD4(+)CD8(+) thymocytes involves upregulation of lineage-specifying transcription factors and transcriptional silencing of CD8 or CD4 coreceptors, respectively, in MHC class II or I (MHCII or I)-restricted thymocytes. In this study, we demonstrate that inactivation of the Dicer RNA endonuclease in murine thymocytes impairs initiation of Cd4 and Cd8 silencing, leading to development of positively selected MHCI- and MHCII-restricted mature CD4(+)CD8(+) thymocytes. Expression of the antiapoptotic BCL2 protein or inactivation of the p53 proapoptotic protein rescues these thymocytes from apoptosis, increasing their frequency and permitting accumulation of CD4(+)CD8(+) αβ T cells in the periphery. Dicer-deficient MHCI-restrict

SUBMITTER: Rupp LJ 

PROVIDER: S-EPMC4185242 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature