10779/crick.11378580.v1
Marcin Łyszkiewicz
Marcin
Łyszkiewicz
Samantha J Winter
Samantha J
Winter
Katrin Witzlau
Katrin
Witzlau
Lisa Föhse
Lisa
Föhse
Rebecca Brownlie
Rebecca
Brownlie
Jacek Puchałka
Jacek
Puchałka
Nikita A Verheyden
Nikita A
Verheyden
Heike Kunze-Schumacher
Heike
Kunze-Schumacher
Esther Imelmann
Esther
Imelmann
Jonas Blume
Jonas
Blume
Solaiman Raha
Solaiman
Raha
Takashi Sekiya
Takashi
Sekiya
Akihiko Yoshimura
Akihiko
Yoshimura
Jochen T Frueh
Jochen T
Frueh
Evelyn Ullrich
Evelyn
Ullrich
Jochen Huehn
Jochen
Huehn
Siegfried Weiss
Siegfried
Weiss
Maximiliano G Gutierrez
Maximiliano G
Gutierrez
Immo Prinz
Immo
Prinz
Rose Zamoyska
Rose
Zamoyska
Natalia Ziętara
Natalia
Ziętara
Andreas Krueger
Andreas
Krueger
miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity
The Francis Crick Institute
2019
Animals
Flow Cytometry
Mice
Mice, Knockout
MicroRNAs
Microscopy, Confocal
Nuclear Receptor Subfamily 4, Group A, Member 1
Nuclear Receptor Subfamily 4, Group A, Member 2
T-Lymphocytes, Regulatory
Thymocytes
Gutierrez FC001092
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
07 Agricultural and Veterinary Sciences
2019-12-17 16:37:21
Journal contribution
https://crick.figshare.com/articles/journal_contribution/miR-181a_b-1_controls_thymic_selection_of_Treg_cells_and_tunes_their_suppressive_capacity/11378580
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.