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Thymic exosomes promote the final maturation of thymocytes

Journal article
Authors Vanja Lundberg
Martin Berglund
Gabriel Skogberg
Susanne Lindgren
Christina Lundqvist
Judith Gudmundsdottir
Karolina Thörn
Esbjörn Telemo
Olov Ekwall
Published in Scientific Reports
Volume 6
ISSN 2045-2322
Publication year 2016
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Clinical Sciences, Department of Pediatrics
Language en
Links dx.doi.org/10.1038/srep36479
Keywords promiscuous gene-expression, dendritic cells, lymphocyte egress, mature, thymocytes, t-cells, tolerance, migration, receptor, antigen, vesicles, Science & Technology - Other Topics
Subject categories Clinical Medicine

Abstract

Extensive knowledge has been gained the last years concerning mechanisms underlying the selection of single positive thymocytes in the thymic medulla. Less is known regarding other important processes in the thymic medulla such as the regulation of late stage thymocyte maturation. We have previously reported that exosomes are abundant in the thymus with a phenotype that indicates an epithelial cell origin and immunoregulatory properties. In this study we use an in vitro system to investigate the effects of thymic exosomes on the maturation of single positive thymocytes as well as effects on nTreg formation. We show that thymic exosomes promote the maturation of single positive CD4(+)CD25(-) cells into mature thymocytes with S1P(1)(+)Qa2(+) and CCR7(+)Qa2(+) phenotypes. Furthermore, we show that thymic exosomes reduce the formation of CD4(+)CD25(+)FoxP3(+) thymocytes and that these exosome effects are independent of dendritic cell co-stimulation but require intact exosomal RNA content and surface proteins. An efficient direct uptake of exosomes by both thymocytes and thymic DC's is also demonstrated. In conclusion, this study demonstrates that exosomes may represent a new route of communication within the thymus.

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