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Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake

by Ziegler, Steven F. , Nakajima, Hiroshi , Endo, Yusuke , Tanaka, Shigeru , Etori, Keishi , Iwata, Arifumi , Suzuki, Harumi , Iwamoto, Taro , Shoda, Jumpei , Hattori, Koto , Kageyama, Takahiro , Yokota, Masaya , Suto, Akira , Kasuya, Tadamichi , Tamura, Jun , Suzuki, Kotaro , Kitajima, Masayuki

in 631/250/1619/554/1898 / 631/250/256 / Adoptive transfer / Antigens / CD4 antigen / Cell activation / Cell differentiation / Cells / Colitis / Cytokines / Epithelial Cells / Fatty acids / Homeostasis / Humanities and Social Sciences / Immunology / Immunoregulation / Inflammatory bowel disease / Large intestine / Lymphatic system / Lymphocytes / Lymphocytes T / Medicine / Molecular modelling / multidisciplinary / Research centers / Science / Science (multidisciplinary) / T-Lymphocytes, Regulatory / Thymic Stromal Lymphopoietin / Thymus / Thymus Gland

2023

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Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake

2023

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2023

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Journal Article

Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake

Ziegler, Steven F.,

Nakajima, Hiroshi,

Endo, Yusuke,

Tanaka, Shigeru,

Etori, Keishi,

Iwata, Arifumi,

Suzuki, Harumi,

Iwamoto, Taro,

Shoda, Jumpei,

Hattori, Koto,

Kageyama, Takahiro,

Yokota, Masaya,

Suto, Akira,

Kasuya, Tadamichi,

Tamura, Jun,

Suzuki, Kotaro,

Kitajima, Masayuki

2023

Overview

Epithelial cells control a variety of immune cells by secreting cytokines to maintain tissue homeostasis on mucosal surfaces. Regulatory T (Treg) cells are essential for immune homeostasis and for preventing tissue inflammation; however, the precise molecular mechanisms by which epithelial cell-derived cytokines function on Treg cells in the epithelial tissues are not well understood. Here, we show that peripheral Treg cells preferentially respond to thymic stromal lymphoprotein (TSLP). Although TSLP does not affect thymic Treg differentiation, TSLP receptor-deficient induced Treg cells derived from naïve CD4 + T cells are less activated in an adoptive transfer model of colitis. Mechanistically, TSLP activates induced Treg cells partially through mTORC1 activation and fatty acid uptake. Thus, TSLP modulates the activation status of induced Treg through the enhanced uptake of fatty acids to maintain homeostasis in the large intestine.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

631/250/1619/554/1898

/ Cell differentiation