| Sažetak: | CD4(+) Foxp3(+) regulatory T cells (Treg) include differentiated populations of effector Treg characterized by the expression of specific transcription factors. Tumors, including intestinal malignancies, often present with local accumulation of Treg that can prevent tumor clearance, but how tumor progression leads to Treg accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition (EMT) and tumor progression, promotes the accumulation of intestinal Treg by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset. Epithelial E-cadherin ablation activates the β-catenin pathway, and we find that increasing β-catenin signals in intestinal epithelial cells also boosts Treg frequencies through local accumulation of KLRG1(+) GATA3(+) Treg. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of IL-33, a cytokine that preferentially expands KLRG1(+) GATA3(+) Treg. Tumors often present reduced E-cadherin expression and increased β-catenin signaling and IL-33 production. Accordingly, Treg accumulation in intestinal tumors from APC(min/+) mice was exclusively due to the increase in KLRG1(+) GATA3(+) Treg. Our data identify a novel axis through which epithelial cells control local Treg cell subsets, which may be activated during intestinal tumorigenesis.
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