TCD8+ suppressor cells produce antigen-specific exosomes carrying miRNA-150 to inhibit contact sensitivity response
-
1
Jagiellonian University College of Medicine, Department of Immunology, Poland
-
2
Yale University School of Medicine, Department of Internal Medicine, United States
INTRODUCTION
T suppressor cells (Ts) release the exosomal suppressor factor (TsF) that inhibit murine contact sensitivity reaction (CS). The antigen specificity of exosomes is warranted by coating with immunoglobulin light chains produced by B1 lymphocytes.
The research is aimed to characterize Ts phenotype and to define the exact structure of exosome cargo conditioning suppressive activity of TsF.
MATERIALS and METHODS
Mice tolerized with high intravenous doses of antigen produce suppressive exosomes isolated in standard ultracentrifugation procedure. Their biological activity is estimated in adoptive transfer of CS effector cells or active hapten immunization and assessed as ear swelling response in CS test. To characterize Ts the negative and positive selection tests and DEREG mice depleted of FoxP3+ T regulatory cells (Tregs) were used. To define the RNA compound of TsF, appropriate miRNA inhibitors and knock-out (KO) mice were used.
RESULTS
TsF exosomes from DEREG mice suppressed CS transfer similarly to wild-type mice. RNA cargo from chromatographically purified suppressive exosomes was sequenced which lead to the assumption that miR150 is the suppressive particle. This hypothesis was verified by using miR150 inhibitor and miR150 KO mice that produce non-suppressive exosomes. Supplementation of exosomes from miR150 KO mice with miR150 restored their suppressive activity.
CONLUSIONS
TsF exosomes are produced by TCD3+CD8+ suppressor lymphocytes that are not Tregs. Their immunoregulatory activity is mediated by miR150 molecules equipped in antigen recognition system. To our knowledge, this is the first evidence of immunoregulation orchestrated in vivo by antigen-specific exosomes carrying inhibitory information coded in a short RNA particle.
Acknowledgements
Acknowledgements:
KB was supported by grants from the Polish Ministry of Science and Higher Education: N401 092 31/2176 and K/ZDS/001429, and PWA by grants from the NIH: AI-076366, AI-07174, and AI-1053786.
Keywords:
TCD8+ suppressor lymphocytes,
miRNA150,
Exosomes,
Immunoregulation,
Immunoglobulin Light Chains
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Bryniarski
K,
Nazimek
K,
Sikora
E,
Ptak
M,
Askenase
PW and
Ptak
W
(2013). TCD8+ suppressor cells produce antigen-specific exosomes carrying miRNA-150 to inhibit contact sensitivity response
.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00077
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
09 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Katarzyna Nazimek, Jagiellonian University College of Medicine, Department of Immunology, Krakow, 31-121, Poland, katarzyna.nazimek@uj.edu.pl