Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung

Akane Suzuki, Chiaki Iwamura, Kenta Shinoda, Damon J. Tumes, Motoko Y. Kimura, Hiroyuki Hosokawa, Yusuke Endo, Shu Horiuchi, Koji Tokoyoda, Haruhiko Koseki, Masakatsu Yamashita, Toshinori Nakayama

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Polycomb group (PcG) gene products regulate the maintenance of homeobox gene expression in Drosophila and vertebrates. In the immune system, PcG molecules control cell cycle progression of thymocytes, Th2 cell differentiation, and the generation of memory CD4 T cells. In this paper, we extended the study of PcG molecules to the regulation of in vivo Th2 responses, especially allergic airway inflammation, by using conditional Ring1B-deficient mice with a CD4 T cell-specific deletion of the Ring1B gene (Ring1B -/- mice). In Ring1B-/- mice, CD4 T cell development appeared to be normal, whereas the differentiation of Th2 cells but not Th1 cells was moderately impaired. In an Ag-induced Th2-driven allergic airway inflammation model, eosinophilic inflammation was attenuated in Ring1B -/- mice. Interestingly, Ring1B-/- effector Th2 cells were highly susceptible to apoptosis in comparison with wild-type effector Th2 cells in vivo and in vitro. The in vitro experiments revealed that the expression of Bim was increased at both the transcriptional and protein levels in Ring1B -/- effector Th2 cells, and the enhanced apoptosis in Ring1B -/- Th2 cells was rescued by the knockdown of Bim but not the other proapoptotic genes, such as Perp, Noxa, or Bax. The enhanced apoptosis detected in the transferred Ring1B-/- Th2 cells in the lung of the recipient mice was also rescued by knockdown of Bim. Therefore, these results indicate that Ring1B plays an important role in Th2-driven allergic airway inflammation through the control of Bim-dependent apoptosis of effector Th2 cells in vivo.

LanguageEnglish
Pages4510-4520
Number of pages11
JournalJournal of Immunology
Volume184
Issue number8
DOIs
Publication statusPublished - 15 Apr 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Suzuki, Akane ; Iwamura, Chiaki ; Shinoda, Kenta ; Tumes, Damon J. ; Kimura, Motoko Y. ; Hosokawa, Hiroyuki ; Endo, Yusuke ; Horiuchi, Shu ; Tokoyoda, Koji ; Koseki, Haruhiko ; Yamashita, Masakatsu ; Nakayama, Toshinori. / Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung. In: Journal of Immunology. 2010 ; Vol. 184, No. 8. pp. 4510-4520.
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title = "Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung",
abstract = "Polycomb group (PcG) gene products regulate the maintenance of homeobox gene expression in Drosophila and vertebrates. In the immune system, PcG molecules control cell cycle progression of thymocytes, Th2 cell differentiation, and the generation of memory CD4 T cells. In this paper, we extended the study of PcG molecules to the regulation of in vivo Th2 responses, especially allergic airway inflammation, by using conditional Ring1B-deficient mice with a CD4 T cell-specific deletion of the Ring1B gene (Ring1B -/- mice). In Ring1B-/- mice, CD4 T cell development appeared to be normal, whereas the differentiation of Th2 cells but not Th1 cells was moderately impaired. In an Ag-induced Th2-driven allergic airway inflammation model, eosinophilic inflammation was attenuated in Ring1B -/- mice. Interestingly, Ring1B-/- effector Th2 cells were highly susceptible to apoptosis in comparison with wild-type effector Th2 cells in vivo and in vitro. The in vitro experiments revealed that the expression of Bim was increased at both the transcriptional and protein levels in Ring1B -/- effector Th2 cells, and the enhanced apoptosis in Ring1B -/- Th2 cells was rescued by the knockdown of Bim but not the other proapoptotic genes, such as Perp, Noxa, or Bax. The enhanced apoptosis detected in the transferred Ring1B-/- Th2 cells in the lung of the recipient mice was also rescued by knockdown of Bim. Therefore, these results indicate that Ring1B plays an important role in Th2-driven allergic airway inflammation through the control of Bim-dependent apoptosis of effector Th2 cells in vivo.",
author = "Akane Suzuki and Chiaki Iwamura and Kenta Shinoda and Tumes, {Damon J.} and Kimura, {Motoko Y.} and Hiroyuki Hosokawa and Yusuke Endo and Shu Horiuchi and Koji Tokoyoda and Haruhiko Koseki and Masakatsu Yamashita and Toshinori Nakayama",
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Suzuki, A, Iwamura, C, Shinoda, K, Tumes, DJ, Kimura, MY, Hosokawa, H, Endo, Y, Horiuchi, S, Tokoyoda, K, Koseki, H, Yamashita, M & Nakayama, T 2010, 'Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung', Journal of Immunology, vol. 184, no. 8, pp. 4510-4520. https://doi.org/10.4049/jimmunol.0903426

Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung. / Suzuki, Akane; Iwamura, Chiaki; Shinoda, Kenta; Tumes, Damon J.; Kimura, Motoko Y.; Hosokawa, Hiroyuki; Endo, Yusuke; Horiuchi, Shu; Tokoyoda, Koji; Koseki, Haruhiko; Yamashita, Masakatsu; Nakayama, Toshinori.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4510-4520.

Research output: Contribution to journalArticle

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T1 - Polycomb group gene product Ring1B regulates Th2-driven airway inflammation through the inhibition of Bim-mediated apoptosis of effector Th2 cells in the lung

AU - Suzuki, Akane

AU - Iwamura, Chiaki

AU - Shinoda, Kenta

AU - Tumes, Damon J.

AU - Kimura, Motoko Y.

AU - Hosokawa, Hiroyuki

AU - Endo, Yusuke

AU - Horiuchi, Shu

AU - Tokoyoda, Koji

AU - Koseki, Haruhiko

AU - Yamashita, Masakatsu

AU - Nakayama, Toshinori

PY - 2010/4/15

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N2 - Polycomb group (PcG) gene products regulate the maintenance of homeobox gene expression in Drosophila and vertebrates. In the immune system, PcG molecules control cell cycle progression of thymocytes, Th2 cell differentiation, and the generation of memory CD4 T cells. In this paper, we extended the study of PcG molecules to the regulation of in vivo Th2 responses, especially allergic airway inflammation, by using conditional Ring1B-deficient mice with a CD4 T cell-specific deletion of the Ring1B gene (Ring1B -/- mice). In Ring1B-/- mice, CD4 T cell development appeared to be normal, whereas the differentiation of Th2 cells but not Th1 cells was moderately impaired. In an Ag-induced Th2-driven allergic airway inflammation model, eosinophilic inflammation was attenuated in Ring1B -/- mice. Interestingly, Ring1B-/- effector Th2 cells were highly susceptible to apoptosis in comparison with wild-type effector Th2 cells in vivo and in vitro. The in vitro experiments revealed that the expression of Bim was increased at both the transcriptional and protein levels in Ring1B -/- effector Th2 cells, and the enhanced apoptosis in Ring1B -/- Th2 cells was rescued by the knockdown of Bim but not the other proapoptotic genes, such as Perp, Noxa, or Bax. The enhanced apoptosis detected in the transferred Ring1B-/- Th2 cells in the lung of the recipient mice was also rescued by knockdown of Bim. Therefore, these results indicate that Ring1B plays an important role in Th2-driven allergic airway inflammation through the control of Bim-dependent apoptosis of effector Th2 cells in vivo.

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