%0 Journal Article %1 SilvaVilches:2017:PLoS-One:28759565 %A Silva-Vilches, C %A Pletinckx, K %A Lohnert, M %A Pavlovic, V %A Ashour, D %A John, V %A Vendelova, E %A Kneitz, S %A Zhou, J %A Chen, R %A Reinheckel, T %A Mueller, T D %A Bodem, J %A Lutz, M B %D 2017 %J PLoS One %K myown tdmueller %N 7 %R 10.1371/journal.pone.0178114 %T Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion %U https://www.ncbi.nlm.nih.gov/pubmed/28759565 %V 12 %X Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CThi conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3+ iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3+ Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.

@article{SilvaVilches:2017:PLoS-One:28759565, abstract = {Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CThi conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3+ iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3+ Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.}, added-at = {2017-08-16T09:33:55.000+0200}, author = {Silva-Vilches, C and Pletinckx, K and Lohnert, M and Pavlovic, V and Ashour, D and John, V and Vendelova, E and Kneitz, S and Zhou, J and Chen, R and Reinheckel, T and Mueller, T D and Bodem, J and Lutz, M B}, biburl = {https://www.bibsonomy.org/bibtex/2aa6ed2052fca861597c3e6dbc450af23/tdmueller}, description = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion. - PubMed - NCBI}, doi = {10.1371/journal.pone.0178114}, interhash = {8fa8cb730a3a299b81334ea34ab5a4f3}, intrahash = {aa6ed2052fca861597c3e6dbc450af23}, journal = {PLoS One}, keywords = {myown tdmueller}, number = 7, pmid = {28759565}, timestamp = {2017-08-16T09:33:55.000+0200}, title = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion}, url = {https://www.ncbi.nlm.nih.gov/pubmed/28759565}, volume = 12, year = 2017 }