Cargando…
Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake
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-deri...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887060/ https://www.ncbi.nlm.nih.gov/pubmed/36717741 http://dx.doi.org/10.1038/s41598-023-28987-1 |
_version_ | 1784880256245563392 |
---|---|
author | Kasuya, Tadamichi Tanaka, Shigeru Tamura, Jun Etori, Keishi Shoda, Jumpei Hattori, Koto Endo, Yusuke Kitajima, Masayuki Kageyama, Takahiro Iwamoto, Taro Yokota, Masaya Iwata, Arifumi Suto, Akira Suzuki, Kotaro Suzuki, Harumi Ziegler, Steven F. Nakajima, Hiroshi |
author_facet | Kasuya, Tadamichi Tanaka, Shigeru Tamura, Jun Etori, Keishi Shoda, Jumpei Hattori, Koto Endo, Yusuke Kitajima, Masayuki Kageyama, Takahiro Iwamoto, Taro Yokota, Masaya Iwata, Arifumi Suto, Akira Suzuki, Kotaro Suzuki, Harumi Ziegler, Steven F. Nakajima, Hiroshi |
author_sort | Kasuya, Tadamichi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9887060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98870602023-02-01 Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake Kasuya, Tadamichi Tanaka, Shigeru Tamura, Jun Etori, Keishi Shoda, Jumpei Hattori, Koto Endo, Yusuke Kitajima, Masayuki Kageyama, Takahiro Iwamoto, Taro Yokota, Masaya Iwata, Arifumi Suto, Akira Suzuki, Kotaro Suzuki, Harumi Ziegler, Steven F. Nakajima, Hiroshi Sci Rep Article 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. Nature Publishing Group UK 2023-01-30 /pmc/articles/PMC9887060/ /pubmed/36717741 http://dx.doi.org/10.1038/s41598-023-28987-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kasuya, Tadamichi Tanaka, Shigeru Tamura, Jun Etori, Keishi Shoda, Jumpei Hattori, Koto Endo, Yusuke Kitajima, Masayuki Kageyama, Takahiro Iwamoto, Taro Yokota, Masaya Iwata, Arifumi Suto, Akira Suzuki, Kotaro Suzuki, Harumi Ziegler, Steven F. Nakajima, Hiroshi Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title | Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title_full | Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title_fullStr | Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title_full_unstemmed | Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title_short | Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake |
title_sort | epithelial cell-derived cytokine tslp activates regulatory t cells by enhancing fatty acid uptake |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887060/ https://www.ncbi.nlm.nih.gov/pubmed/36717741 http://dx.doi.org/10.1038/s41598-023-28987-1 |
work_keys_str_mv | AT kasuyatadamichi epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT tanakashigeru epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT tamurajun epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT etorikeishi epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT shodajumpei epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT hattorikoto epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT endoyusuke epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT kitajimamasayuki epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT kageyamatakahiro epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT iwamototaro epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT yokotamasaya epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT iwataarifumi epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT sutoakira epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT suzukikotaro epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT suzukiharumi epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT zieglerstevenf epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake AT nakajimahiroshi epithelialcellderivedcytokinetslpactivatesregulatorytcellsbyenhancingfattyaciduptake |