Human thymic epithelial primary cells produce exosomes carrying tissue‐restricted antigens

Abstract

Exosomes are nano-sized vesicles released by cells into the extracellular space and have been shown to be present in thymic tissue both in mice and in humans. The source of thymic exosomes is however still an enigma and hence it is not known whether thymic epithelial cells (TECs) are able to produce exosomes. In this work, we have cultured human TECs and isolated exosomes. These exosomes carry tissue-restricted antigens (TRAs), for example, myelin basic protein and desmoglein 3. The presence of TRAs indicates a possible role for thymic epithelium-derived exosomes in the selection process of thymocytes. The key contribution of these exosomes could be to disseminate self-antigens from the thymic epithelia, thus making them more accessible to the pool of maturing thymocytes. This would increase the coverage of TRAs within the thymus, and facilitate the process of positive and negative selection.

Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

“…As an important example, T regulatory (Treg) Foxp3 pos cells produce exosomes that suppress Th1 cell proliferation and cytokine production via gene silencing due to transferred Treg cell-derived miRNAs [58]. Further, thymic epithelial cells produce exosomes carrying tissue-restricted Ag that guide development of the Treg cells [59,60]. …”

“…Ts [2] and Treg [58] cell-derived exosome inhibition of effector Th1 cells, c . thymic epithelial cell-derived, Ag carrying exosome mediated maturation of Treg cells [59,60], d . DC activation of other DC and also B cells [50], e .…”

Development and regulation of exosome‐based therapy products

“…Many cell types actively secrete exosomes, in particular, cells of the immune system such as dendritic cells (DCs), macrophages, B cells, and T cells, as well as mesenchymal stem cells (MSCs), endothelial cells, and epithelial cells . Exosomes and other types of microvesicles are also secreted by a variety of cancer cells .…”

Reinforcing the ‘gauntlet’ of thymic negative selection via exosomal transfer of self‐antigens

“…Exosomes have been reported to have a role in diverse settings, such as cancer, malaria infection and gestational tolerance. In this issue, Skogberg et al 1 provide evidence that exosomes from the thymic epithelium may have an important role in negative selection, potentially broadening the availability of peripheral self‐antigens to other antigen‐presenting cells (APCs).…”