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

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miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity. / Łyszkiewicz, Marcin; Winter, Samantha J; Witzlau, Katrin; Föhse, Lisa; Brownlie, Rebecca; Puchałka, Jacek; Verheyden, Nikita A; Kunze-Schumacher, Heike; Imelmann, Esther; Blume, Jonas; Raha, Solaiman; Sekiya, Takashi; Yoshimura, Akihiko; Frueh, Jochen T; Ullrich, Evelyn; Huehn, Jochen; Weiss, Siegfried; Gutierrez, Maximiliano G; Prinz, Immo; Zamoyska, Rose; Ziętara, Natalia; Krueger, Andreas.

In: PLOS BIOL, Vol. 17, No. 3, 03.2019, p. e2006716.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Łyszkiewicz, M, Winter, SJ, Witzlau, K, Föhse, L, Brownlie, R, Puchałka, J, Verheyden, NA, Kunze-Schumacher, H, Imelmann, E, Blume, J, Raha, S, Sekiya, T, Yoshimura, A, Frueh, JT, Ullrich, E, Huehn, J, Weiss, S, Gutierrez, MG, Prinz, I, Zamoyska, R, Ziętara, N & Krueger, A 2019, 'miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity', PLOS BIOL, vol. 17, no. 3, pp. e2006716. https://doi.org/10.1371/journal.pbio.2006716

APA

Łyszkiewicz, M., Winter, S. J., Witzlau, K., Föhse, L., Brownlie, R., Puchałka, J., Verheyden, N. A., Kunze-Schumacher, H., Imelmann, E., Blume, J., Raha, S., Sekiya, T., Yoshimura, A., Frueh, J. T., Ullrich, E., Huehn, J., Weiss, S., Gutierrez, M. G., Prinz, I., ... Krueger, A. (2019). miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity. PLOS BIOL, 17(3), e2006716. https://doi.org/10.1371/journal.pbio.2006716

Vancouver

Łyszkiewicz M, Winter SJ, Witzlau K, Föhse L, Brownlie R, Puchałka J et al. miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity. PLOS BIOL. 2019 Mar;17(3):e2006716. https://doi.org/10.1371/journal.pbio.2006716

Bibtex

@article{6efa512ca0ca464e919e01601d075ea9,
title = "miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity",
abstract = "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.",
keywords = "Animals, Flow Cytometry, Mice, Mice, Knockout, MicroRNAs/genetics, Microscopy, Confocal, Nuclear Receptor Subfamily 4, Group A, Member 1/genetics, Nuclear Receptor Subfamily 4, Group A, Member 2/genetics, T-Lymphocytes, Regulatory/metabolism, Thymocytes/metabolism",
author = "Marcin {\L}yszkiewicz and Winter, {Samantha J} and Katrin Witzlau and Lisa F{\"o}hse and Rebecca Brownlie and Jacek Pucha{\l}ka and Verheyden, {Nikita A} and Heike Kunze-Schumacher and Esther Imelmann and Jonas Blume and Solaiman Raha and Takashi Sekiya and Akihiko Yoshimura and Frueh, {Jochen T} and Evelyn Ullrich and Jochen Huehn and Siegfried Weiss and Gutierrez, {Maximiliano G} and Immo Prinz and Rose Zamoyska and Natalia Zi{\c e}tara and Andreas Krueger",
year = "2019",
month = mar,
doi = "10.1371/journal.pbio.2006716",
language = "English",
volume = "17",
pages = "e2006716",
journal = "PLOS BIOL",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity

AU - Łyszkiewicz, Marcin

AU - Winter, Samantha J

AU - Witzlau, Katrin

AU - Föhse, Lisa

AU - Brownlie, Rebecca

AU - Puchałka, Jacek

AU - Verheyden, Nikita A

AU - Kunze-Schumacher, Heike

AU - Imelmann, Esther

AU - Blume, Jonas

AU - Raha, Solaiman

AU - Sekiya, Takashi

AU - Yoshimura, Akihiko

AU - Frueh, Jochen T

AU - Ullrich, Evelyn

AU - Huehn, Jochen

AU - Weiss, Siegfried

AU - Gutierrez, Maximiliano G

AU - Prinz, Immo

AU - Zamoyska, Rose

AU - Ziętara, Natalia

AU - Krueger, Andreas

PY - 2019/3

Y1 - 2019/3

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.

AB - 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 - Animals

KW - Flow Cytometry

KW - Mice

KW - Mice, Knockout

KW - MicroRNAs/genetics

KW - Microscopy, Confocal

KW - Nuclear Receptor Subfamily 4, Group A, Member 1/genetics

KW - Nuclear Receptor Subfamily 4, Group A, Member 2/genetics

KW - T-Lymphocytes, Regulatory/metabolism

KW - Thymocytes/metabolism

U2 - 10.1371/journal.pbio.2006716

DO - 10.1371/journal.pbio.2006716

M3 - SCORING: Journal article

C2 - 30856173

VL - 17

SP - e2006716

JO - PLOS BIOL

JF - PLOS BIOL

SN - 1544-9173

IS - 3

ER -