miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity

  • The interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1–deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte–associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.
Metadaten
Author:Marcin Łyszkiewicz, Samantha J. Winter, Katrin Witzlau, Lisa Föhse, Rebecca Brownlie, Jacek Puchałka, Nikita A. Verheyden, Heike Kunze-SchumacherGND, Esther Imelmann, Jonas Blume, Solaiman Raha, Takashi Sekiya, Akihiko Yoshimura, Jochen Früh, Evelyn UllrichORCiDGND, Jochen Hühn, Siegfried Weiss, Maximiliano Gutierrez, Immo Prinz, Rose Zamoyska, Natalia Karolina Zie̜tara, Andreas Krueger
URN:urn:nbn:de:hebis:30:3-484719
DOI:https://doi.org/10.1371/journal.pbio.2006716
ISSN:1545-7885
ISSN:1544-9173
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30856173
Parent Title (English):PLoS biology
Publisher:PLoS
Place of publication:Lawrence, KS
Contributor(s):Avinash Bhandoola
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/03/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/26
Tag:Forkhead box; MicroRNAs; Regulatory T cells; T cell receptors; T cells; TCR signaling cascade; Thymocytes; Thymus
Volume:17
Issue:(3): e2006716
Page Number:27
First Page:1
Last Page:27
Note:
Copyright: © 2019 Łyszkiewicz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:448057204
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0