Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells

TLDR

The immune synapse facilitates communication between T cells and antigen‑presenting cells, and recent evidence shows that exosomes can transfer RNA, including microRNAs, between cells. The study aims to determine whether miRNAs are exchanged during cognate immune interactions and to demonstrate antigen‑driven, unidirectional transfer from T cells to APCs. The authors show that CD63⁺ exosomes are delivered at the immune synapse, mediating the transfer of miRNAs from T cells to APCs. The results reveal that T‑cell exosomes contain distinct miRNA repertoires, that inhibition of neutral sphingomyelinase‑2 blocks their transfer to APCs, and that the transferred miRNAs modulate recipient gene expression, confirming antigen‑dependent, unidirectional miRNA transfer via exosomes during immune synapsis.

Abstract

The immune synapse is an exquisitely evolved means of communication between T cells and antigen-presenting cells (APCs) during antigen recognition. Recent evidence points to the transfer of RNA via exosomes as a novel mode of intercellular communication. Here we show that exosomes of T, B and dendritic immune cells contain microRNA (miRNA) repertoires that differ from those of their parent cells. We investigate whether miRNAs are exchanged during cognate immune interactions, and demonstrate the existence of antigen-driven unidirectional transfer of miRNAs from the T cell to the APC, mediated by the delivery of CD63+ exosomes on immune synapse formation. Inhibition of exosome production by targeting neutral sphingomyelinase-2 impairs transfer of miRNAs to APCs. Moreover, miRNAs transferred during immune synapsis are able to modulate gene expression in recipient cells. Thus, our results support a mechanism of cellular communication involving antigen-dependent, unidirectional intercellular transfer of miRNAs by exosomes during immune synapsis. Exosomes released from cells can transfer RNA to recipient cells. In this study, the authors demonstrate that microRNAs in exosomes from T cells can be transferred to antigen-presenting cells during immune synapsis, and that this can alter gene expression, suggesting a new form of cellular communication.