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The interleukin-33 receptor ST2 is important for the development of peripheral airway hyperresponsiveness and inflammation in a house dust mite mouse model of asthma.
Clin Exp Allergy 2016; 46(3):479-90CE

Abstract

BACKGROUND

Several clinical and experimental studies have implicated IL-33 and its receptor ST2 in the development of asthma. However, the effect of IL-33/ST2 signalling on airway responses and inflammation in allergic asthma is not well established.

OBJECTIVE

To investigate the role of IL-33/ST2 signalling in promoting allergen-induced airway hyperresponsiveness (AHR), airway inflammation, antigen-specific IgE production and mast cell activity in a mouse model of asthma.

METHODS

ST2-deficient (ST2(-/-)) mice and control BALB/c mice were given house dust mite (HDM) extract over a 6-week period. Forty-eight hours after the final HDM administration, lung function and airway inflammation were evaluated. Airway responsiveness was determined in the central airways and peripheral lung. Cellular infiltration and mast cell protease mMCP-1 levels were quantified in bronchoalveolar lavage fluid (BALF). Recruitment of inflammatory cells and inflammatory cytokine profiles were assessed in pulmonary tissue, and HDM-specific IgE was measured in serum.

RESULTS

ST2 deficiency diminished HDM-induced AHR in the peripheral lung, while AHR in the central airways was unaffected. Inflammatory responses to HDM were also reduced in ST2(-/-) mice as reflected by the lower induction of HDM-specific serum IgE, inhibition of HDM-induced eosinophilia and reduced macrophage count in BALF, and a diminished influx of inflammatory cells and reduced goblet cell hyperplasia around the peripheral airways. Furthermore, the levels of the inflammatory cytokines IL-1β, IL-5, IL-13, IL-33, GM-CSF, thymic stromal lymphopoietin and mast cell protease mMCP-1 were reduced in HDM-treated ST2(-/-) mice compared with wild-type controls.

CONCLUSIONS

In addition to promoting Th2 inflammation, we now suggest a role for the IL-33/ST2 pathway for the induction of peripheral inflammation and mucus production that causes AHR in the peripheral lung. This mechanism for inducing AHR at distal parts of the lung may be of specific importance as asthma is considered as a small airway disease.

Authors+Show Affiliations

Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ALK-Abelló, Hoersholm, Denmark.Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26609909

Citation

Zoltowska, A M., et al. "The Interleukin-33 Receptor ST2 Is Important for the Development of Peripheral Airway Hyperresponsiveness and Inflammation in a House Dust Mite Mouse Model of Asthma." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 46, no. 3, 2016, pp. 479-90.
Zoltowska AM, Lei Y, Fuchs B, et al. The interleukin-33 receptor ST2 is important for the development of peripheral airway hyperresponsiveness and inflammation in a house dust mite mouse model of asthma. Clin Exp Allergy. 2016;46(3):479-90.
Zoltowska, A. M., Lei, Y., Fuchs, B., Rask, C., Adner, M., & Nilsson, G. P. (2016). The interleukin-33 receptor ST2 is important for the development of peripheral airway hyperresponsiveness and inflammation in a house dust mite mouse model of asthma. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 46(3), pp. 479-90. doi:10.1111/cea.12683.
Zoltowska AM, et al. The Interleukin-33 Receptor ST2 Is Important for the Development of Peripheral Airway Hyperresponsiveness and Inflammation in a House Dust Mite Mouse Model of Asthma. Clin Exp Allergy. 2016;46(3):479-90. PubMed PMID: 26609909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The interleukin-33 receptor ST2 is important for the development of peripheral airway hyperresponsiveness and inflammation in a house dust mite mouse model of asthma. AU - Zoltowska,A M, AU - Lei,Y, AU - Fuchs,B, AU - Rask,C, AU - Adner,M, AU - Nilsson,G P, PY - 2014/09/19/received PY - 2015/11/20/revised PY - 2015/11/22/accepted PY - 2015/11/27/entrez PY - 2015/11/27/pubmed PY - 2016/12/15/medline KW - AHR KW - IL-33 KW - ST2 KW - asthma SP - 479 EP - 90 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 46 IS - 3 N2 - BACKGROUND: Several clinical and experimental studies have implicated IL-33 and its receptor ST2 in the development of asthma. However, the effect of IL-33/ST2 signalling on airway responses and inflammation in allergic asthma is not well established. OBJECTIVE: To investigate the role of IL-33/ST2 signalling in promoting allergen-induced airway hyperresponsiveness (AHR), airway inflammation, antigen-specific IgE production and mast cell activity in a mouse model of asthma. METHODS: ST2-deficient (ST2(-/-)) mice and control BALB/c mice were given house dust mite (HDM) extract over a 6-week period. Forty-eight hours after the final HDM administration, lung function and airway inflammation were evaluated. Airway responsiveness was determined in the central airways and peripheral lung. Cellular infiltration and mast cell protease mMCP-1 levels were quantified in bronchoalveolar lavage fluid (BALF). Recruitment of inflammatory cells and inflammatory cytokine profiles were assessed in pulmonary tissue, and HDM-specific IgE was measured in serum. RESULTS: ST2 deficiency diminished HDM-induced AHR in the peripheral lung, while AHR in the central airways was unaffected. Inflammatory responses to HDM were also reduced in ST2(-/-) mice as reflected by the lower induction of HDM-specific serum IgE, inhibition of HDM-induced eosinophilia and reduced macrophage count in BALF, and a diminished influx of inflammatory cells and reduced goblet cell hyperplasia around the peripheral airways. Furthermore, the levels of the inflammatory cytokines IL-1β, IL-5, IL-13, IL-33, GM-CSF, thymic stromal lymphopoietin and mast cell protease mMCP-1 were reduced in HDM-treated ST2(-/-) mice compared with wild-type controls. CONCLUSIONS: In addition to promoting Th2 inflammation, we now suggest a role for the IL-33/ST2 pathway for the induction of peripheral inflammation and mucus production that causes AHR in the peripheral lung. This mechanism for inducing AHR at distal parts of the lung may be of specific importance as asthma is considered as a small airway disease. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/26609909/The_interleukin_33_receptor_ST2_is_important_for_the_development_of_peripheral_airway_hyperresponsiveness_and_inflammation_in_a_house_dust_mite_mouse_model_of_asthma_ L2 - https://doi.org/10.1111/cea.12683 DB - PRIME DP - Unbound Medicine ER -