TY  - JOUR
A1  - Riquelme, Paloma
A1  - Haarer, Jan
A1  - Kammler, Anja
A1  - Walter, Lisa
A1  - Tomiuk, Stefan
A1  - Ahrens, Norbert
A1  - Wege, Anja K.
A1  - Goecze, Ivan
A1  - Zecher, Daniel
A1  - Banas, Bernhard
A1  - Spang, Rainer
A1  - Fändrich, Fred
A1  - Lutz, Manfred B.
A1  - Sawitzki, Birgit
A1  - Schlitt, Hans J.
A1  - Ochando, Jordi
A1  - Geissler, Edward K.
A1  - Hutchinson, James A.
T1  - TIGIT\(^+\) iTregs elicited by human regulatory macrophages control T cell immunity
JF  - Nature Communications
N2  - 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-beta, 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.
KW  - Allotransplantation
KW  - Immunosuppression
KW  - Monocytes and macrophages
KW  - Regulatory T cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226321
VL  - 9
IS  - 9
ER  -