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The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells

Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3(+) Tregs from naïve CD4(+) T cells in the local tumor microenvironment. T...

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Autores principales: MaruYama, Takashi, Kobayashi, Shuhei, Nakatsukasa, Hiroko, Moritoki, Yuki, Taguchi, Daiki, Sunagawa, Yoichi, Morimoto, Tatsuya, Asao, Atsuko, Jin, Wenwen, Owada, Yuji, Ishii, Naoto, Iwabuchi, Yoshiharu, Yoshimura, Akihiko, Chen, WanJun, Shibata, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261301/
https://www.ncbi.nlm.nih.gov/pubmed/34248973
http://dx.doi.org/10.3389/fimmu.2021.687669
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author MaruYama, Takashi
Kobayashi, Shuhei
Nakatsukasa, Hiroko
Moritoki, Yuki
Taguchi, Daiki
Sunagawa, Yoichi
Morimoto, Tatsuya
Asao, Atsuko
Jin, Wenwen
Owada, Yuji
Ishii, Naoto
Iwabuchi, Yoshiharu
Yoshimura, Akihiko
Chen, WanJun
Shibata, Hiroyuki
author_facet MaruYama, Takashi
Kobayashi, Shuhei
Nakatsukasa, Hiroko
Moritoki, Yuki
Taguchi, Daiki
Sunagawa, Yoichi
Morimoto, Tatsuya
Asao, Atsuko
Jin, Wenwen
Owada, Yuji
Ishii, Naoto
Iwabuchi, Yoshiharu
Yoshimura, Akihiko
Chen, WanJun
Shibata, Hiroyuki
author_sort MaruYama, Takashi
collection PubMed
description Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3(+) Tregs from naïve CD4(+) T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3(+) Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability.
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spelling pubmed-82613012021-07-08 The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells MaruYama, Takashi Kobayashi, Shuhei Nakatsukasa, Hiroko Moritoki, Yuki Taguchi, Daiki Sunagawa, Yoichi Morimoto, Tatsuya Asao, Atsuko Jin, Wenwen Owada, Yuji Ishii, Naoto Iwabuchi, Yoshiharu Yoshimura, Akihiko Chen, WanJun Shibata, Hiroyuki Front Immunol Immunology Regulatory T cells (Tregs) play a crucial role in preventing antitumor immune responses in cancer tissues. Cancer tissues produce large amounts of transforming growth factor beta (TGF-β), which promotes the generation of Foxp3(+) Tregs from naïve CD4(+) T cells in the local tumor microenvironment. TGF-β activates nuclear factor kappa B (NF-κB)/p300 and SMAD signaling, which increases the number of acetylated histones at the Foxp3 locus and induces Foxp3 gene expression. TGF-β also helps stabilize Foxp3 expression. The curcumin analog and antitumor agent, GO-Y030, prevented the TGF-β-induced generation of Tregs by preventing p300 from accelerating NF-κB-induced Foxp3 expression. Moreover, the addition of GO-Y030 resulted in a significant reduction in the number of acetylated histones at the Foxp3 promoter and at the conserved noncoding sequence 1 regions that are generated in response to TGF-β. In vivo tumor models demonstrated that GO-Y030-treatment prevented tumor growth and reduced the Foxp3(+) Tregs population in tumor-infiltrating lymphocytes. Therefore, GO-Y030 exerts a potent anticancer effect by controlling Treg generation and stability. Frontiers Media S.A. 2021-06-23 /pmc/articles/PMC8261301/ /pubmed/34248973 http://dx.doi.org/10.3389/fimmu.2021.687669 Text en Copyright © 2021 MaruYama, Kobayashi, Nakatsukasa, Moritoki, Taguchi, Sunagawa, Morimoto, Asao, Jin, Owada, Ishii, Iwabuchi, Yoshimura, Chen and Shibata https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
MaruYama, Takashi
Kobayashi, Shuhei
Nakatsukasa, Hiroko
Moritoki, Yuki
Taguchi, Daiki
Sunagawa, Yoichi
Morimoto, Tatsuya
Asao, Atsuko
Jin, Wenwen
Owada, Yuji
Ishii, Naoto
Iwabuchi, Yoshiharu
Yoshimura, Akihiko
Chen, WanJun
Shibata, Hiroyuki
The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title_full The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title_fullStr The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title_full_unstemmed The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title_short The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells
title_sort curcumin analog go-y030 controls the generation and stability of regulatory t cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261301/
https://www.ncbi.nlm.nih.gov/pubmed/34248973
http://dx.doi.org/10.3389/fimmu.2021.687669
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