Thymic exosomes promote the final maturation of thymocytes.
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 S1P1+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.
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.|Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Vanja
V
Lundberg
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Martin
M
Berglund
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Gabriel
G
Skogberg
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.|Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Susanne
S
Lindgren
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Christina
C
Lundqvist
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.|Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Judith
J
Gudmundsdottir
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Karolina
K
Thörn
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
Esbjörn
E
Telemo
Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.|Dept of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Olov
O
Ekwall
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D053645:Interleukin-2 Receptor alpha Subunit; D035683:MicroRNAs; C032907:Q surface antigens; D054400:Receptors, CCR7