TY  - JOUR
A1  - Łyszkiewicz, Marcin
A1  - Winter, Samantha J.
A1  - Witzlau, Katrin
A1  - Föhse, Lisa
A1  - Brownlie, Rebecca
A1  - Puchałka, Jacek
A1  - Verheyden, Nikita A.
A1  - Kunze-Schumacher, Heike
A1  - Imelmann, Esther
A1  - Blume, Jonas
A1  - Raha, Solaiman
A1  - Sekiya, Takashi
A1  - Yoshimura, Akihiko
A1  - Früh, Jochen
A1  - Ullrich, Evelyn
A1  - Hühn, Jochen
A1  - Weiss, Siegfried
A1  - Gutierrez, Maximiliano
A1  - Prinz, Immo
A1  - Zamoyska, Rose
A1  - Zie̜tara, Natalia Karolina
A1  - Krueger, Andreas
T1  - miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity
T2  - PLoS biology
N2  - 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.
KW  - Regulatory T cells
KW  - T cell receptors
KW  - TCR signaling cascade
KW  - T cells
KW  - Thymocytes
KW  - MicroRNAs
KW  - Thymus
KW  - Forkhead box
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48471
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-484719
SN  - 1545-7885
SN  - 1544-9173
N1  - 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.
VL  - 17
IS  - (3): e2006716
SP  - 1
EP  - 27
PB  - PLoS
CY  - Lawrence, KS
ER  -