9 research outputs found
Biologics and postbiologics: novel immunotherapeutics for the induction and maintenance of remission.
Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis.
Autologous bone marrow transplantation in autoimmune arthritis restores immune homeostasis through CD4+ CD25+ Foxp3+ regulatory T cells.
CD30 discriminates heat shock protein 60-induced FOXP3 +CD4+ T cells with a regulatory phenotype.
Canonical Wnt Signaling Negatively Modulates Regulatory T Cell Function
Foxp3 is crucial for both the development and
function of regulatory T (Treg) cells; however, the
posttranslational mechanisms regulating Foxp3
transcriptional output remain poorly defined. Here,
we demonstrate that T cell factor 1 (TCF1) and
Foxp3 associates in Treg cells and that active Wnt
signaling disrupts Foxp3 transcriptional activity. A
global chromatin immunoprecipitation sequencing
comparison in Treg cells revealed considerable
overlap between Foxp3 and Wnt target genes. The
activation of Wnt signaling reduced Treg-mediated
suppression both in vitro and in vivo, whereas
disruption of Wnt signaling in Treg cells enhanced
their suppressive capacity. The activation of effector
T cells increased Wnt3a production, and Wnt3a
levels were found to be greatly increased in mononuclear
cells isolated from synovial fluid versus
peripheral blood of arthritis patients. We propose a
model in which Wnt produced under inflammatory
conditions represses Treg cell function, allowing a
productive immune response, but, if uncontrolled,
could lead to the development of autoimmunity