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oai:repisalud.isciii.es:20.500.12105/103942024-09-27T22:36:27Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Riquelme, Paloma author Haarer, Jan author Kammler, Anja author Walter, Lisa author Tomiuk, Stefan author Ahrens, Norbert author Wege, Anja K author Goecze, Ivan author Zecher, Daniel author Banas, Bernhard author Spang, Rainer author Fändrich, Fred author Lutz, Manfred B author Sawitzki, Birgit author Schlitt, Hans J author Ochando, Jordi author Geissler, Edward K author Hutchinson, James A author 2018 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 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-β, 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. Nat Commun . 2018 Jul 20;9(1):2858. 10.1038/s41467-018-05167-8 2041-1723 Nature communications 30030423 http://hdl.handle.net/20.500.12105/10394 TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.