Chae, Wook-Jin Park, Jong-Hyun Henegariu, Octavian Yilmaz, Saliha Hao, Liming Bothwell, Alfred L. M. 2024-01-20T00:31:46Z 2024-01-20T00:31:46Z 2021-09-05 2017-10 0019-2805 https://pubs.kist.re.kr/handle/201004/122232 Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3(+) regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4(+) T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3(+) Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3(+) Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3(+) Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. English WILEY WNT ANTAGONIST DICKKOPF-1 MASTER REGULATOR EXPRESSION RECEPTOR THERAPY DKK1 Membrane-bound Dickkopf-1 in Foxp3(+) regulatory T cells suppresses T-cell-mediated autoimmune colitis Article 10.1111/imm.12766 1 IMMUNOLOGY, v.152, no.2, pp.265 - 275 IMMUNOLOGY 152 2 265 275 scie scopus 000409491800009 2-s2.0-85021374064 Immunology Immunology Article WNT ANTAGONIST DICKKOPF-1 MASTER REGULATOR EXPRESSION RECEPTOR THERAPY DKK1 autoimmune colitis Dickkopf-1 regulatory T cells