Chronic inflammation increases the sensitivity of mouse Treg for TNFR2 costimulation

Please always quote using this URN: urn:nbn:de:bvb:20-opus-173259
  • TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. \(In\) \(vitro\), TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported \(in\) \(vitro\) expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of boneTNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. \(In\) \(vitro\), TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported \(in\) \(vitro\) expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function. \(In\) \(vivo\) application of TNCscTNF80-induced mild myelopoiesis in naïve mice without affecting the immune cell composition. Already a single application expanded Treg cells and improved suppression of CD4 T cells in mice with chronic inflammation. By contrast, multiple applications of the TNFR2 agonist were required to expand Treg cells in naïve mice. Improved suppression of T cell proliferation depended on expression of TNFR2 by T cells in mice repeatedly treated with TNCscTNF80, without a major contribution of TNFR2 on myeloid cells. Thus, TNFR2 activation on T cells in naïve mice can lead to immune suppression \(in\) \(vivo\). These findings support the important role of TNFR2 for Treg cells in immune regulation.show moreshow less

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Metadaten
Author: Tobias Schmid, Lena Falter, Sabine Weber, Nils Müller, Konstantin Molitor, David Zeller, Dorothea Weber-Steffens, Thomas Hehlgans, Harald Wajant, Sven Mostböck, Daniela N. Männel
URN:urn:nbn:de:bvb:20-opus-173259
Document Type:Journal article
Faculties:Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Language:English
Parent Title (English):Frontiers in Immunology
Year of Completion:2017
Volume:8
Article Number:1471
Source:Frontiers in Immunology (2017) 8:1471. https://doi.org/10.3389/fimmu.2017.01471
DOI:https://doi.org/10.3389/fimmu.2017.01471
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29163535
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:MDSC; TNFR2; costimulation; immune regulation; inflammation; molecular medicine; regulatory T cell
Release Date:2021/06/24
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International