Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism

Yen Leong Chua, Ka Hang Liong, Chiung Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I. Chun Kuo, Yongliang Zhang, W. S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Franciska Haczku, Veronique Angeli, Paul A. MacAry, Kaw Yan Chua, David M. Kemeny

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13-dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.

Original languageEnglish (US)
Pages (from-to)3771-3781
Number of pages11
JournalJournal of Immunology
Volume197
Issue number10
DOIs
StatePublished - Nov 15 2016

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Th2 Cells
Interleukin-13
Interleukin-4
Asthma
Lung
Allergens
Job Syndrome
Lymph Nodes
Lung Compliance
Goblet Cells
Forced Expiratory Volume
Eosinophilia
Mucus
Body Temperature
Inhalation
Transgenic Mice
Smooth Muscle Myocytes
Hyperplasia
Immune System
Collagen

ASJC Scopus subject areas

  • Immunology

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Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism. / Chua, Yen Leong; Liong, Ka Hang; Huang, Chiung Hui; Wong, Hok Sum; Zhou, Qian; Ler, Say Siong; Tang, Yafang; Low, Chin Pei; Koh, Hui Yu; Kuo, I. Chun; Zhang, Yongliang; Wong, W. S Fred; Peh, Hong Yong; Lim, Hwee Ying; Ge, Moyar Qing; Haczku, Angela Franciska; Angeli, Veronique; MacAry, Paul A.; Chua, Kaw Yan; Kemeny, David M.

In: Journal of Immunology, Vol. 197, No. 10, 15.11.2016, p. 3771-3781.

Research output: Contribution to journalArticle

Chua, YL, Liong, KH, Huang, CH, Wong, HS, Zhou, Q, Ler, SS, Tang, Y, Low, CP, Koh, HY, Kuo, IC, Zhang, Y, Wong, WSF, Peh, HY, Lim, HY, Ge, MQ, Haczku, AF, Angeli, V, MacAry, PA, Chua, KY & Kemeny, DM 2016, 'Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism', Journal of Immunology, vol. 197, no. 10, pp. 3771-3781. https://doi.org/10.4049/jimmunol.1502676
Chua, Yen Leong ; Liong, Ka Hang ; Huang, Chiung Hui ; Wong, Hok Sum ; Zhou, Qian ; Ler, Say Siong ; Tang, Yafang ; Low, Chin Pei ; Koh, Hui Yu ; Kuo, I. Chun ; Zhang, Yongliang ; Wong, W. S Fred ; Peh, Hong Yong ; Lim, Hwee Ying ; Ge, Moyar Qing ; Haczku, Angela Franciska ; Angeli, Veronique ; MacAry, Paul A. ; Chua, Kaw Yan ; Kemeny, David M. / Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism. In: Journal of Immunology. 2016 ; Vol. 197, No. 10. pp. 3771-3781.
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abstract = "Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13-dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.",
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T1 - Blomia tropicalis-specific TCR transgenic Th2 cells induce inducible BALT and severe asthma in mice by an IL-4/IL-13-dependent mechanism

AU - Chua, Yen Leong

AU - Liong, Ka Hang

AU - Huang, Chiung Hui

AU - Wong, Hok Sum

AU - Zhou, Qian

AU - Ler, Say Siong

AU - Tang, Yafang

AU - Low, Chin Pei

AU - Koh, Hui Yu

AU - Kuo, I. Chun

AU - Zhang, Yongliang

AU - Wong, W. S Fred

AU - Peh, Hong Yong

AU - Lim, Hwee Ying

AU - Ge, Moyar Qing

AU - Haczku, Angela Franciska

AU - Angeli, Veronique

AU - MacAry, Paul A.

AU - Chua, Kaw Yan

AU - Kemeny, David M.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13-dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.

AB - Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13-dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.

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