TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.

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 t...

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Detalles Bibliográficos
Autores: 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, Ochando, Jordi, Geissler, Edward K, Hutchinson, James A
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10394
Acceso en línea:http://hdl.handle.net/20.500.12105/10394
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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.

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