Transient Depletion of Foxp3 Regulatory T Cells Selectively Promotes Aggressive β Cell Autoimmunity in Genetically Susceptible DEREG Mice.

Type 1 diabetes (T1D) represents a hallmark of the fatal multiorgan autoimmune syndrome affecting humans with abrogated Foxp3 regulatory T (Treg) cell function due to gene mutations, but whether the loss of Foxp3 Treg cell activity is indeed sufficient to promote β cell autoimmunity requires further scrutiny. As opposed to human Treg cell deficiency, β cell autoimmunity has not been observed in non-autoimmune-prone mice with constitutive deficiency or after diphtheria toxin receptor (DTR)-mediated ablation of Foxp3 Treg cells. In the spontaneous nonobese diabetic (NOD) mouse model of T1D, constitutive Foxp3 deficiency did not result in invasive insulitis and hyperglycemia, and previous studies on Foxp3 Treg cell ablation focused on Foxp3 NOD mice, in which expression of a transgenic BDC2.

Wnt3a/β-Catenin Signaling Conditions Differentiation of Partially Exhausted T-effector Cells in Human Cancers.

In this study, we investigated the role of the Wnt/β-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and β-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4 or CD8 T cells.