Publication: TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity.
Loading...
Identifiers
Publication date
2018
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Metrics
Export
Abstract
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.
Description
Keywords
MeSH Terms
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
DeCS Terms
Bibliographic citation
Nat Commun . 2018 Jul 20;9(1):2858.