Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways

Ji Hwan Ryu, Jung Yeon Yoo, Min Ji Kim, Sang Gyu Hwang, Kwang Chul Ahn, Jae Chan Ryu, Mi Kyung Choi, Jung Hee Joo, Chang Hoon Kim, Sang Nam Lee, Won Jae Lee, Jaesang Kim, Dong Min Shin, Mi Na Kweon, Yun Soo Bae, Joo Heon Yoon

Research output: Contribution to journalArticle

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Abstract

Background: Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective: We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively. Methods: We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results: HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation. Conclusions: We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.

Original languageEnglish
Pages (from-to)549-561
Number of pages13
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

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Pyroglyphidae
Toll-Like Receptor 2
Glucans
Asthma
Innate Immunity
Nose
Nasal Mucosa
Lung
Reactive Oxygen Species
Oxidoreductases
Mucous Membrane
Epithelium
Epithelial Cells
Allergic Rhinitis
Lipids

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ryu, Ji Hwan ; Yoo, Jung Yeon ; Kim, Min Ji ; Hwang, Sang Gyu ; Ahn, Kwang Chul ; Ryu, Jae Chan ; Choi, Mi Kyung ; Joo, Jung Hee ; Kim, Chang Hoon ; Lee, Sang Nam ; Lee, Won Jae ; Kim, Jaesang ; Shin, Dong Min ; Kweon, Mi Na ; Bae, Yun Soo ; Yoon, Joo Heon. / Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. In: Journal of Allergy and Clinical Immunology. 2013 ; Vol. 131, No. 2. pp. 549-561.
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title = "Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways",
abstract = "Background: Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective: We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively. Methods: We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results: HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation. Conclusions: We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.",
author = "Ryu, {Ji Hwan} and Yoo, {Jung Yeon} and Kim, {Min Ji} and Hwang, {Sang Gyu} and Ahn, {Kwang Chul} and Ryu, {Jae Chan} and Choi, {Mi Kyung} and Joo, {Jung Hee} and Kim, {Chang Hoon} and Lee, {Sang Nam} and Lee, {Won Jae} and Jaesang Kim and Shin, {Dong Min} and Kweon, {Mi Na} and Bae, {Yun Soo} and Yoon, {Joo Heon}",
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Ryu, JH, Yoo, JY, Kim, MJ, Hwang, SG, Ahn, KC, Ryu, JC, Choi, MK, Joo, JH, Kim, CH, Lee, SN, Lee, WJ, Kim, J, Shin, DM, Kweon, MN, Bae, YS & Yoon, JH 2013, 'Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways', Journal of Allergy and Clinical Immunology, vol. 131, no. 2, pp. 549-561. https://doi.org/10.1016/j.jaci.2012.07.050

Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. / Ryu, Ji Hwan; Yoo, Jung Yeon; Kim, Min Ji; Hwang, Sang Gyu; Ahn, Kwang Chul; Ryu, Jae Chan; Choi, Mi Kyung; Joo, Jung Hee; Kim, Chang Hoon; Lee, Sang Nam; Lee, Won Jae; Kim, Jaesang; Shin, Dong Min; Kweon, Mi Na; Bae, Yun Soo; Yoon, Joo Heon.

In: Journal of Allergy and Clinical Immunology, Vol. 131, No. 2, 01.02.2013, p. 549-561.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways

AU - Ryu, Ji Hwan

AU - Yoo, Jung Yeon

AU - Kim, Min Ji

AU - Hwang, Sang Gyu

AU - Ahn, Kwang Chul

AU - Ryu, Jae Chan

AU - Choi, Mi Kyung

AU - Joo, Jung Hee

AU - Kim, Chang Hoon

AU - Lee, Sang Nam

AU - Lee, Won Jae

AU - Kim, Jaesang

AU - Shin, Dong Min

AU - Kweon, Mi Na

AU - Bae, Yun Soo

AU - Yoon, Joo Heon

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background: Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective: We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively. Methods: We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results: HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation. Conclusions: We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.

AB - Background: Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different. Objective: We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively. Methods: We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts. Results: HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation. Conclusions: We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.

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