담배연기에 의한 선천성 면역반응 자극 및 천식의 발생과 악화
Cigarette smoke extract contributes to the inception and aggravation of asthmatic inflammation by stimulating innate immunity
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Purpose: Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. Methods: Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4+ T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. Results: Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4+ T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3+ in CD4+ T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII+ DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17+ ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. Conclusion: In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.
Abstract
Purpose: Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. Methods: Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4+ T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. Results: Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4+ T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3+ in CD4+ T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII+ DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17+ ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. Conclusion: In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.
참고문헌 (31)
- Fahy JV, "Type 2 inflammation in asthma--present in most, absent in many", Nat Rev Immunol, 15, pp.57~65 (2015)
- Boonpiyathad T, "Immunologic mechanisms in asthma", Semin Immunol, 46, pp.101333~ (2019)
- Douwes J, "Non-eosinophilic asthma : importance and possible mechanisms", Thorax, 57, pp.643~648 (2002)
- Lee J, "Cigarette smoking and inflammation : cellular and molecular mechanisms", J Dent Res, 91, pp.142~149 (2012)
- Thomson NC, "Asthma and cigarette smoking", Eur Respir J, 24, pp.822~833 (2004)
- Jing W, "Passive smoking induces pediatric asthma by affecting the balance of Treg", Th17 cells, 2019, pp.85, 469~476
- Siew LQC, "Cigarette smoking increases bronchial mucosal IL-17A expression in asthmatics, which acts in concert with environmental aeroallergens to engender neutrophilic inflammation", Clin Exp Allergy, 47, pp.740~750 (2017)
- Doe C, "Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD", Chest, 138, pp.1140~1147 (2010)
- Kim HY, "Innate lymphoid cells in asthma : will they take your breath away?", Eur J Immunol, 46, pp.795~806 (2016)
- Kim J, "Innate immune crosstalk in asthmatic airways : Innate lymphoid cells coordinate polarization of lung macrophages", J Allergy Clin Immunol, 143, pp.1769~1782 (2019)
- Lee HS, "Critical role of interleukin-23 in development of asthma promoted by cigarette smoke", J Mol Med(Berl), 97, pp.937~949 (2019)
- Lee HS, "Thalidomide inhibits alternative activation of macrophages in vivo and in vitro : a potential mechanism of anti-asthmatic effect of thalidomide", PLoS One, 10, pp.e0123094~ (2015)
- Shim JS, "Aggravation of asthmatic inflammation by chlorine exposure via innate lymphoid cells and CD11c(intermediate)macrophages", Allergy, 75, pp.381~391 (2020)
- Clarke DL, "Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation", Mucosal Immunol, 7, pp.558~567 (2014)
- Kool M, "Cutting edge : alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome", J Immunol, 181, pp.3755~3759 (2008)
- Nakamura Y, "Cigarette smoke extract induces thymic stromal lymphopoietin expression, leading to T(H)2-type immune responses and airway inflammation", J Allergy Clin Immunol, 122, pp.1208~1214 (2008)
- Bhalla DK, "Cigarette smoke, inflammation, and lung injury : a mechanistic perspective", J Toxicol Environ Health B Crit Rev, 12, pp.45~64 (2009)
- Churg A, "Mechanisms of cigarette smoke-induced COPD : insights from animal models", Am J Physiol Lung Cell Mol Physiol, 294, pp.L612~L631 (2008)
- Tu X, "Asthma-COPD overlap : current understanding and the utility of experimental models", Eur Respir Rev, 30, pp.190185~ (2021)
- To T, "Progression from asthma to chronic obstructive pulmonary disease. Is air pollution a risk factor?", Am J Respir Crit Care Med, 194, pp.429~438 (2016)
- Strzelak A, "Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases : a mechanistic review", Int J Environ Res Public Health, 15, pp.1033~ (2018)
- 장안수, "The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics", Journal of Korean Medical Science, 24(2), pp.209~214 (2009), 대한의학회
- Panda SK, "Innate lymphoid cells in mucosal immunity", Front Immunol, 10, pp.861~ (2019)
- Kim M, "Cigarette smoke induces intestinal inflammation via a Th17 cell-neutrophil axis", Front Immunol, 10, pp.75~ (2019)
- Shikhagaie MM, "Neuropilin-1 is expressed on lymphoid tissue residing LTi-like group 3 innate lymphoid cells and associated with ectopic lymphoid aggregates", Cell Rep, 18, pp.1761~1773 (2017)
- Blomme EE, "Quantification and role of innate lymphoid cell subsets in chronic obstructive pulmonary disease", Clin Transl Immunology, 10, pp.e1287~ (2021)
- Silver JS, "Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs", Nat Immunol, 17, pp.626~635 (2016)
- Hussell T, "Alveolar macrophages : plasticity in a tissue-specific context", Nat Rev Immunol, 14, pp.81~93 (2014)
- Oriss TB, "IRF5 distinguishes severe asthma in humans and drives Th1 phenotype and airway hyperreactivity in mice", JCI Insight, 2, pp.e91019~ (2017)
- Liu T, "FIZZ2", RELM-β induction and role in pulmonary fibrosis, 2011, pp.187, 450~461
- Conrad ML, "Comparison of adjuvant and adjuvant-free murine experimental asthma models", Clin Exp Allergy, 39, pp.1246~1254 (2009)