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2016 ; 6
(ä): 36479
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Thymic exosomes promote the final maturation of thymocytes
#MMPMID27824109
Lundberg V
; Berglund M
; Skogberg G
; Lindgren S
; Lundqvist C
; Gudmundsdottir J
; Thörn K
; Telemo E
; Ekwall O
Sci Rep
2016[Nov]; 6
(ä): 36479
PMID27824109
show ga
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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