Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/10394
TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.
Riquelme, Paloma | Haarer, Jan | Kammler, Anja | Walter, Lisa | Tomiuk, Stefan | Ahrens, Norbert | Wege, Anja K | Goecze, Ivan | Zecher, Daniel | Banas, Bernhard | Spang, Rainer | Fändrich, Fred | Lutz, Manfred B | Sawitzki, Birgit | Schlitt, Hans J | Cano-Ochando, Jordi ISCIII | Geissler, Edward K | Hutchinson, James A
Nat Commun . 2018 Jul 20;9(1):2858.
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.
Allografts | Animals | Cell Differentiation | Dendritic Cells | Forkhead Transcription Factors | Graft Rejection | Humans | Interleukin-10 | Kidney Transplantation | Lipopolysaccharide Receptors | Macrophages | Mice | Phenotype | Receptors, Immunologic | Signal Transduction | T-Lymphocytes, Regulatory | Transforming Growth Factor beta | Transplantation, Homologous
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