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Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism

CD4(+) memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation re...

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Autores principales: Kokubo, Kota, Hirahara, Kiyoshi, Kiuchi, Masahiro, Tsuji, Kaori, Shimada, Yuki, Sonobe, Yuri, Shinmi, Rie, Hishiya, Takahisa, Iwamura, Chiaki, Onodera, Atsushi, Nakayama, Toshinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926250/
https://www.ncbi.nlm.nih.gov/pubmed/36595680
http://dx.doi.org/10.1073/pnas.2218345120
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author Kokubo, Kota
Hirahara, Kiyoshi
Kiuchi, Masahiro
Tsuji, Kaori
Shimada, Yuki
Sonobe, Yuri
Shinmi, Rie
Hishiya, Takahisa
Iwamura, Chiaki
Onodera, Atsushi
Nakayama, Toshinori
author_facet Kokubo, Kota
Hirahara, Kiyoshi
Kiuchi, Masahiro
Tsuji, Kaori
Shimada, Yuki
Sonobe, Yuri
Shinmi, Rie
Hishiya, Takahisa
Iwamura, Chiaki
Onodera, Atsushi
Nakayama, Toshinori
author_sort Kokubo, Kota
collection PubMed
description CD4(+) memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation remain unclear. We found that reactive oxygen species (ROS) metabolism changed dramatically in T helper-2 (Th2) cells during the contraction phase in the process of memory T cell formation. Thioredoxin-interacting protein (Txnip), a regulator of oxidoreductase, regulated apoptosis by scavenging ROS via the nuclear factor erythroid 2-related factor 2 (Nrf2)–biliverdin reductase B (Blvrb) pathway. Txnip regulated the pathology of chronic airway inflammation in the lung by controlling the generation of allergen-specific pathogenic memory Th2 cells in vivo. Thus, the Txnip–Nrf2–Blvrb axis directs ROS metabolic reprogramming in Th2 cells and is a potential therapeutic target for intractable chronic inflammatory diseases.
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spelling pubmed-99262502023-07-03 Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism Kokubo, Kota Hirahara, Kiyoshi Kiuchi, Masahiro Tsuji, Kaori Shimada, Yuki Sonobe, Yuri Shinmi, Rie Hishiya, Takahisa Iwamura, Chiaki Onodera, Atsushi Nakayama, Toshinori Proc Natl Acad Sci U S A Biological Sciences CD4(+) memory T cells are central to long-lasting protective immunity and are involved in shaping the pathophysiology of chronic inflammation. While metabolic reprogramming is critical for the generation of memory T cells, the mechanisms controlling the redox metabolism in memory T cell formation remain unclear. We found that reactive oxygen species (ROS) metabolism changed dramatically in T helper-2 (Th2) cells during the contraction phase in the process of memory T cell formation. Thioredoxin-interacting protein (Txnip), a regulator of oxidoreductase, regulated apoptosis by scavenging ROS via the nuclear factor erythroid 2-related factor 2 (Nrf2)–biliverdin reductase B (Blvrb) pathway. Txnip regulated the pathology of chronic airway inflammation in the lung by controlling the generation of allergen-specific pathogenic memory Th2 cells in vivo. Thus, the Txnip–Nrf2–Blvrb axis directs ROS metabolic reprogramming in Th2 cells and is a potential therapeutic target for intractable chronic inflammatory diseases. National Academy of Sciences 2023-01-03 2023-01-10 /pmc/articles/PMC9926250/ /pubmed/36595680 http://dx.doi.org/10.1073/pnas.2218345120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Kokubo, Kota
Hirahara, Kiyoshi
Kiuchi, Masahiro
Tsuji, Kaori
Shimada, Yuki
Sonobe, Yuri
Shinmi, Rie
Hishiya, Takahisa
Iwamura, Chiaki
Onodera, Atsushi
Nakayama, Toshinori
Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title_full Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title_fullStr Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title_full_unstemmed Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title_short Thioredoxin-interacting protein is essential for memory T cell formation via the regulation of the redox metabolism
title_sort thioredoxin-interacting protein is essential for memory t cell formation via the regulation of the redox metabolism
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926250/
https://www.ncbi.nlm.nih.gov/pubmed/36595680
http://dx.doi.org/10.1073/pnas.2218345120
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