Immunostimulatory activity of murine keratinocyte-derived exosomes.
It has long been known that keratinocytes influence cutaneous immunity through secretion of soluble factors. Exosomes, small membrane vesicles of endocytotic origin, have been implicated in intercellular communication processes such as the transfer of tumor cell antigens and the activation of recipient dendritic cells (DC). However, little is known about immunomodulatory functions of keratinocyte-derived exosomes. To address this question, we analysed exosome secretion of the murine keratinocyte cell line MPEK under steady state as well as inflammatory conditions (+/- IFNγ). These exosomes were readily taken up by bone marrow-derived DC (BMDC) in vitro resulting in a matured phenotype, as evidenced by increased CD40 expression as well as by the production of large amounts of IL-6, IL-10 and IL-12. When the transfer of antigen-specific information through exosomes was investigated, it was found that keratinocytes took up antigen (ovalbumin) and transferred it to their exosomes. However, these antigen-harbouring exosomes failed to induce antigen-specific T cell responses via BMDC. Together, this novel biological function suggests that keratinocytes are able to direct unspecific immune processes but do not elicit specific immune responses.
Department of Dermatology, Venereology, and Allergology, Georg August University, Göttingen, Germany.
Kristina
K
Kotzerke
Martin
M
Mempel
Thiha
T
Aung
Gerald G
GG
Wulf
Henning
H
Urlaub
Dirk
D
Wenzel
Michael P
MP
Schön
Andrea
A
Braun
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism*; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D010047:Ovalbumin / Q000378:metabolism; D010641:Phenotype; D040901:Proteomics; D013601:T-Lymphocytes / Q000166:cytology
D000941:Antigens; D019013:CD40 Antigens; D015850:Interleukin-6; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin
exosomes; innate immunity; keratinocytes; skin