Premium
Membrane‐bound Dickkopf‐1 in Foxp3 + regulatory T cells suppresses T‐cell‐mediated autoimmune colitis
Author(s) -
Chae WookJin,
Park JongHyun,
Henegariu Octavian,
Yilmaz Saliha,
Hao Liming,
Bothwell Alfred L. M.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12766
Subject(s) - foxp3 , microbiology and biotechnology , il 2 receptor , t cell , colitis , regulatory t cell , biology , wnt signaling pathway , immunology , chemistry , signal transduction , immune system
Summary 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 CD 4 + T‐cell proliferation, resulting in CD 4 T‐cell‐mediated autoimmune colitis. Thymus‐derived Treg cells showed a robust expression of DKK ‐1 but not in naive or effector CD 4 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.