T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma

Atsushi Moriwaki, Hiromasa Inoue, Takako Nakano, Yuko Matsunaga, Yukiko Matsuno, Takafumi Matsumoto, Satoru Fukuyama, Keiko Kan-o, Koichiro Matsumoto, Miyuki Tsuda-Eguchi, Daisuke Nagakubo, Osamu Yoshie, Akihiko Yoshimura, Masato Kubo, Yoichi Nakanishi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

CD4+ T cells, particularly T helper (Th) 2 cells, play a pivotal role in the pathophysiology of allergic asthma. Suppressor of cytokine signaling (SOCS) proteins control the balance of CD4+ T cell differentiation. Mice that lack SOCS3 in T cells by crossing SOCS3-floxed mice with Lck-Cre-transgenic mice have reduced allergen-induced eosinophilia in the airways. Here, we studied the effects of SOCS3 silencing with small interfering (si) RNA in primary CD4+ T cells on Th2 cell differentiation and on asthmatic responses in mice. Th2 cells were generated from ovalbumin (OVA)-specific T cell receptor-transgenic mice in vitroandtransferred into recipient mice. Transfection of SOCS3-specific siRNA attenuated Th2 response in vitro. Adoptive transfer of SOCS3-siRNAT cells exhibited markedly suppressed airway hyperresponsiveness and eosinophilia after OVA challenge, with a concomitant decrease in OVA-specific CD4+ T cell accumulation in the airways. To investigate the mechanism of this impaired CD4+ T cell accumulation, we inactivated SOCS3 of T cells by crossing SOCS3-floxed (SOCS3 flox/flox) mice with CD4-Cre transgenic mice. CD4-Cre x SOCS3 flox/flox mice exhibited fewer IL-4-producing cells and more reduced eosinophil infiltration in bronchoalveolar lavage fluids than control mice in a model of OVA-induced asthma. Expression of CCR3 and CCR4 in CD4+ T cells was decreased in CD4-Cre x SOCS3flox/flox mice. CCR4 expression was also decreased in CD4+ T cells after transfer of SOCS3 siRNA-treated T cells. These findings suggest that the therapeutic modulation of SOCS3 expression in CD4+ T cells might be effective in preventing the development of allergic asthma.

Original languageEnglish
Pages (from-to)448-455
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number4
DOIs
Publication statusPublished - 2011 Apr 1

Fingerprint

T-cells
Small Interfering RNA
Asthma
Cytokines
T-Lymphocytes
Ovalbumin
Th2 Cells
Therapeutics
Transgenic Mice
Eosinophilia
Cell Differentiation
Suppressor of Cytokine Signaling Proteins
Adoptive Transfer
Bronchoalveolar Lavage Fluid
T-Cell Antigen Receptor
Infiltration
Eosinophils
Interleukin-4
Allergens
Transfection

Keywords

  • Allergy
  • Lung
  • Signal transduction
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma. / Moriwaki, Atsushi; Inoue, Hiromasa; Nakano, Takako; Matsunaga, Yuko; Matsuno, Yukiko; Matsumoto, Takafumi; Fukuyama, Satoru; Kan-o, Keiko; Matsumoto, Koichiro; Tsuda-Eguchi, Miyuki; Nagakubo, Daisuke; Yoshie, Osamu; Yoshimura, Akihiko; Kubo, Masato; Nakanishi, Yoichi.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 44, No. 4, 01.04.2011, p. 448-455.

Research output: Contribution to journalArticle

Moriwaki, A, Inoue, H, Nakano, T, Matsunaga, Y, Matsuno, Y, Matsumoto, T, Fukuyama, S, Kan-o, K, Matsumoto, K, Tsuda-Eguchi, M, Nagakubo, D, Yoshie, O, Yoshimura, A, Kubo, M & Nakanishi, Y 2011, 'T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma', American Journal of Respiratory Cell and Molecular Biology, vol. 44, no. 4, pp. 448-455. https://doi.org/10.1165/rcmb.2009-0051OC
Moriwaki, Atsushi ; Inoue, Hiromasa ; Nakano, Takako ; Matsunaga, Yuko ; Matsuno, Yukiko ; Matsumoto, Takafumi ; Fukuyama, Satoru ; Kan-o, Keiko ; Matsumoto, Koichiro ; Tsuda-Eguchi, Miyuki ; Nagakubo, Daisuke ; Yoshie, Osamu ; Yoshimura, Akihiko ; Kubo, Masato ; Nakanishi, Yoichi. / T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma. In: American Journal of Respiratory Cell and Molecular Biology. 2011 ; Vol. 44, No. 4. pp. 448-455.
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AU - Matsumoto, Koichiro

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