Marcin Łyszkiewicz, Samantha J. Winter, Katrin Witzlau, Lisa Föhse, Rebecca Brownlie, Jacek Puchałka, Nikita A. Verheyden, Heike Kunze-Schumacher, Esther Imelmann, Jonas Blume, Solaiman Raha, Takashi Sekiya, Akihiko Yoshimura, Jochen Früh, Evelyn Ullrich, Jochen Hühn, Siegfried Weiss, Maximiliano Gutierrez, Immo Prinz, Rose Zamoyska, Natalia Karolina Zie̜tara, Andreas Krueger
- 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.
MetadatenAuthor: | Marcin ŁyszkiewiczGND, Samantha J. WinterORCiDGND, Katrin Witzlau, Lisa FöhseGND, Rebecca Brownlie, Jacek Puchałka, Nikita A. VerheydenORCiD, Heike Kunze-SchumacherORCiDGND, Esther Imelmann, Jonas BlumeGND, Solaiman Raha, Takashi Sekiya, Akihiko Yoshimura, Jochen Früh, Evelyn UllrichORCiDGND, Jochen Hühn, Siegfried Weiss, Maximiliano Gutierrez, Immo PrinzORCiDGND, Rose Zamoyska, Natalia Karolina Zie̜tara, Andreas KruegerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-484719 |
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DOI: | https://doi.org/10.1371/journal.pbio.2006716 |
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ISSN: | 1545-7885 |
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ISSN: | 1544-9173 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30856173 |
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Parent Title (English): | PLoS biology |
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Publisher: | PLoS |
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Place of publication: | Lawrence, KS |
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Contributor(s): | Avinash Bhandoola |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2019 |
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Date of first Publication: | 2019/03/11 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/03/26 |
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Tag: | Forkhead box; MicroRNAs; Regulatory T cells; T cell receptors; T cells; TCR signaling cascade; Thymocytes; Thymus |
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Volume: | 17 |
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Issue: | (3): e2006716 |
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Page Number: | 27 |
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First Page: | 1 |
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Last Page: | 27 |
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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. |
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HeBIS-PPN: | 448057204 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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