TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-20

AUTHORS

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

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. More... »

PAGES

2858

References to SciGraph publications

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

9

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-05167-8

DOI

http://dx.doi.org/10.1038/s41467-018-05167-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105609580

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30030423


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