TIGIT\(^+\) iTregs elicited by human regulatory macrophages control T cell immunity
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-226321
- Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4(+) T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4(+) T cells to IL-10-producing, TIGIT(+) FoxP3(+)-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs reliesHuman regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4(+) T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4(+) T cells to IL-10-producing, TIGIT(+) FoxP3(+)-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-beta, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT(+) Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct-pathway Tregs.…
Autor(en): | Paloma Riquelme, Jan Haarer, Anja Kammler, Lisa Walter, Stefan Tomiuk, Norbert Ahrens, Anja K. Wege, Ivan Goecze, Daniel Zecher, Bernhard Banas, Rainer Spang, Fred Fändrich, Manfred B. Lutz, Birgit Sawitzki, Hans J. Schlitt, Jordi Ochando, Edward K. Geissler, James A. Hutchinson |
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URN: | urn:nbn:de:bvb:20-opus-226321 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Nature Communications |
Erscheinungsjahr: | 2018 |
Band / Jahrgang: | 9 |
Heft / Ausgabe: | 9 |
Seitenangabe: | 2858, 1-18 |
Originalveröffentlichung / Quelle: | Nature Communications | (2018) 9:2858 |
DOI: | https://doi.org/10.1038/s41467-018-05167-8 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Allotransplantation; Immunosuppression; Monocytes and macrophages; Regulatory T cells |
Datum der Freischaltung: | 14.03.2023 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |