Tumour-associated changes in intestinal epithelial cells cause local 
accumulation of KLRG1+ GATA3+ regulatory T cells in mice

Meinicke, Holger; Bremser, Anna; Brack, Maria; Akeus, Paulina; Pearson, Claire; Bullers, Samuel; Hoffmeyer, Katrin; Stemmler, Marc P.; Quiding-Järbrink, Marianne; Izcue, Ana

doi:10.1111/imm.12750

Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG₁⁺ GATA₃⁺ regulatory T cells in mice

Meinicke, H., Bremser, A., Brack, M., Akeus, P., Pearson, C., Bullers, S., Hoffmeyer, K., Stemmler, M. P., Quiding-Järbrink, M., & Izcue, A. (2017). Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG₁⁺ GATA₃⁺ regulatory T cells in mice. Immunology, 74-88. doi:10.1111/imm.12750.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-0000-BF72-9 版のパーマリンク: https://hdl.handle.net/21.11116/0000-0008-9A6B-3

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Meinicke, Holger^{1, 2}, 著者
Bremser, Anna¹, 著者
Brack, Maria^{1, 2}, 著者
Akeus, Paulina², 著者
Pearson, Claire², 著者
Bullers, Samuel², 著者
Hoffmeyer, Katrin¹, 著者
Stemmler, Marc P.¹, 著者
Quiding-Järbrink, Marianne², 著者
Izcue, Ana¹, 著者

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1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640
2External Organizations, ou_persistent22

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キーワード: cell surface molecules, mucosa, regulatory T cells, tumour immunology

要旨: CD4⁺ Foxp3⁺ regulatory T (Treg) cells include differentiated populations of effector Treg cells characterized by the expression of specific transcription factors. Tumours, including intestinal malignancies, often present with local accumulation of Treg cells that can prevent tumour clearance, but how tumour progression leads to Treg cell 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 and tumour progression, promotes the accumulation of intestinal Treg cells 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 cell frequencies through local accumulation of KLRG1⁺ GATA3⁺ Treg cells. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of interleukin-33, a cytokine that preferentially expands KLRG1⁺ GATA3⁺ Treg cells. Tumours often present reduced E-cadherin expression and increased β-catenin signalling and interleukin-33 production. Accordingly, Treg cell accumulation in intestinal tumours from APC^min/+ mice was exclusively due to the increase in KLRG1⁺ GATA3⁺Treg cells. 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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言語: eng - English

日付: オンライン出版: 2017-04-24

出版の状態: オンラインで出版済み

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識別子（DOI, ISBNなど）: DOI: 10.1111/imm.12750

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出版物名: Immunology

その他 : Immunology

種別: 学術雑誌

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出版社, 出版地: Oxford : Blackwell Scientific Publications.

ページ: - 巻号: - 通巻号: - 開始・終了ページ: 74 - 88 識別子（ISBN, ISSN, DOIなど）: ISSN: 0019-2805
CoNE: https://pure.mpg.de/cone/journals/resource/954925405692

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