Thymic epithelial cells require lipid kinase Vps34 for CD4 but not CD8 T cell selection.

The generation of a functional, self-tolerant T cell receptor (TCR) repertoire depends on interactions between developing thymocytes and antigen-presenting thymic epithelial cells (TECs). Cortical TECs (cTECs) rely on unique antigen-processing machinery to generate self-peptides specialized for T cell positive selection. In our current study, we focus on the lipid kinase Vps34, which has been implicated in autophagy and endocytic vesicle trafficking. We show that loss of Vps34 in TECs causes profound defects in the positive selection of the CD4 T cell lineage but not the CD8 T cell lineage. Utilizing TCR sequencing, we show that T cell selection in conditional mutants causes altered repertoire properties including reduced clonal sharing. cTECs from mutant mice display an increased abundance of invariant chain intermediates bound to surface MHC class II molecules, indicating altered antigen processing. Collectively, these studies identify lipid kinase Vps34 as an important contributor to the repertoire of selecting ligands processed and presented by TECs to developing CD4 T cells.

Secret messengers: Extracellular RNA communication in the immune system.

One of the hallmarks of the immune system is a dynamic landscape of cellular communication through the secretion of soluble factors, production of cell-bound ligands, and expression of surface receptors. This communication affects all aspects of immune cell behavior, integrates the responses of immune cells in tissues, and is fundamental to orchestrating effective immunity. Recent pioneering work has shown that the transfer of ribonucleic acids (RNAs) constitutes a novel mode of cellular communication. This communication involves diverse RNA species, with short noncoding RNAs especially enriched in the extracellular space. These RNAs are highly stable and selectively packaged for secretion. Transferred RNAs have functions in target cells that both mirror their cell-intrinsic roles and adopt novel mechanisms of action. These extracellular RNAs both impact the behavior of individual immune cells and participate in local and systemic immune responses. The impacts of RNA communication on immune cells and disease states have important implications for the development of novel clinical biomarkers and innovative therapeutic designs in immune-related disease. In this review, we will discuss the foundation of knowledge that is establishing RNA communication as an active and functional process in the immune system.