%0 Journal Article
%T ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20171352
%X Long-term immunity depends partly on the establishment of memory CD8+ T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor ¦Â (TGF-¦Â) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8+ T cells. TGF-¦Â induced and sustained Zeb1 expression in maturing memory CD8+ T cells. Meanwhile, both TGF-¦Â and miR-200 family members selectively inhibited Zeb2. Additionally, the miR-200 family was necessary for optimal memory CD8+ T cell formation. These data outline a previously unknown genetic pathway in CD8+ T cells that controls effector and memory cell fate decisions.
%U http://jem.rupress.org/content/215/4/1153