UC San Diego

The RNA binding protein, DDX5, is a polyfunctional regulator of gene expression, yet its role in CD8+ T cell biology has not been extensively investigated. In this study, we demonstrate that deletion of Ddx5 reduced differentiation of terminal effector (TE), effector memory (TEM), and terminal effector memory (t-TEM) cells while increasing the generation of central memory (TCM) cells. In addition, DDX5 deficiency also increases the proportion of CD69+ CD103+ tissue-resident memory (TRM) cells and promotes Eomes and CD122 expression in established TRM cells from the small intestine intraepithelial layer (IEL). Single-cell CITE-sequencing analyses revealed increased expression of genes that promote TCM cell differentiation, including Tcf7 and Eomes, in response to deletion of Ddx5. Moreover, we have shown a putative association between DDX5 and components of the polycomb repressive complex 2 (PRC2) in in vitro activated CD8+ T cells indicating that DDX5 may mediate histone methylation at memory gene loci. Together, these findings uncover a role for DDX5 in regulating the differentiation of CD8+ T cell subsets in response to microbial infection.