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  - 
TY  - JOUR
A1  - Vendelova, Emilia
A1  - Ashour, Diyaaeldin
A1  - Blank, Patrick
A1  - Erhard, Florian
A1  - Saliba, Antoine-Emmanuel
A1  - Kalinke, Ulrich
A1  - Lutz, Manfred B.
T1  - Tolerogenic transcriptional signatures of steady-state and pathogen-induced dendritic cells
JF  - Frontiers in Immunology
N2  - Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses. One such strategy is characterized by adopting the host's T cell tolerance mechanisms. Understanding these tolerogenic mechanisms is of utmost importance for therapeutic approaches to treat immune pathologies, tumors and infections. Transcriptional profiling has developed into a potent tool for DC subset identification. Here, we review and compile pathogen-induced tolerogenic transcriptional signatures from mRNA profiling data of currently available bacterial- or helminth-induced transcriptional signatures. We compare them with signatures of tolerogenic steady-state DC subtypes to identify common and divergent strategies of pathogen induced immune evasion. Candidate molecules are discussed in detail. Our analysis provides further insights into tolerogenic DC signatures and their exploitation by different pathogens.
KW  - bacteria
KW  - helminths
KW  - immune evasion
KW  - mycobacteria
KW  - transcriptional profiling
KW  - tolerogenic dendritic cells
KW  - steady-state dendritic cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175636
VL  - 9
IS  - 333
ER  -