Cigarette Smoke Extract Contributes to the Inception and Aggravation of Asthmatic Inflammation by Stimulating Innate Immunity

JMDS

Journal of Medicines Development Sciences

2382-63632382-6371

WHIOCE PUBLISHING PTE. LTD.

10.18063/jmds.v8i1.143

Article

Cigarette Smoke Extract Contributes to the Inception and Aggravation of Asthmatic Inflammation by Stimulating Innate Immunityhttps://artdesignp.com/journal/JMDS/8/1/10.18063/jmds.v8i1.143KimYujin,KimJeonghyeon,MoYosep,ParkDa Eun,LeeHyun-Seung,JungJae-Woo,KangHye-Ryun

2023

2023-08-25

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.

Fahy JV, 2015, Type 2 Inflammation in Asthma - Present in Most, Absent in Many. Nat Rev Immunol, 15(1): 57–65. Boonpiyathad T, Sözener ZC, Satitsuksanoa P, et al, 2019, Immunologic Mechanisms in Asthma. Semin Immunol, 46: 101333. Douwes J, Gibson P, Pekkanen J, et al, 2002, Non-Eosinophilic Asthma: Importance and Possible Mechanisms. Thorax, 57(7): 643–648. Lee J, Taneja V, Vassallo R, 2012, Cigarette Smoking and Inflammation: Cellular and Molecular Mechanisms. J Dent Res, 91(2): 142–149. Thomson NC, Chaudhuri R, Livingston E, 2004, Asthma and Cigarette Smoking. Eur Respir J, 24(5): 822–833. Jing W, Wang W, Liu Q, 2019, Passive Smoking Induces Pediatric Asthma by Affecting the Balance of Treg/Th17 Cells. Pediatr Res, 85(4): 469–476. Siew LQC, Wu S-Y, Ying S, et al, 2017, 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(6): 740–750. Doe C, Bafadhel M, Siddiqui S, et al, 2010, Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD. Chest, 138(5): 1140–1147. Kim HY, Umetsu DT, Dekruyff RH, 2016, Innate Lymphoid Cells in Asthma: Will They Take Your Breath Away? Eur J Immunol, 46(4): 795–806. Kim J, Chang Y, Bae B, et al, 2019, Innate Immune Crosstalk in Asthmatic Airways: Innate Lymphoid Cells Coordinate Polarization of Lung Macrophages. J Allergy Clin Immunol, 143(5): 1769–1782.e11. Lee HS, Park D-E, Lee J-W, et al, 2019, Critical Role of Interleukin-23 in Development of Asthma Promoted by Cigarette Smoke. J Mol Med (Berl), 97(7): 937–949. Lee HS, Kwon H-S, Park D-E, et al, 2015, Thalidomide Inhibits Alternative Activation of Macrophages in Vivo and in Vitro: A Potential Mechanism of Anti-Asthmatic Effect of Thalidomide. PLoS One, 10(4): e0123094. Shim J-S, Lee H-S, Park D-E, et al, 2020, Aggravation of Asthmatic Inflammation by Chlorine Exposure via Innate Lymphoid Cells and CD11cintermediate Macrophages. Allergy, 75(2): 381–391. Clarke DL, Davis NHE, Campion CL, et al, 2013, Dectin-2 Sensing of House Dust Mite is Critical for the Initiation of Airway Inflammation. Mucosal Immunol, 7(3): 558–567. Kool M, Pétrilli V, De Smedt T, et al, 2008, Cutting Edge: Alum Adjuvant Stimulates Inflammatory Dendritic Cells Through Activation of the NALP3 Inflammasome. J Immunol, 181(6): 3755–3759. Nakamura Y, Miyata M, Ohba T, et al, 2008, Cigarette Smoke Extract Induces Thymic Stromal Lymphopoietin Expression, Leading to T(H)2-Type Immune Responses and Airway Inflammation. J Allergy Clin Immunol, 122(6): 1208–1214. Bhalla DK, Hirata F, Rishi AK, et al, 2009, Cigarette Smoke, Inflammation, and Lung Injury: A Mechanistic Perspective. J Toxicol Environ Health B Crit Rev, 12(1): 45–64. Churg A, Cosio M, Wright JL, 2008, Mechanisms Of Cigarette Smoke-Induced COPD: Insights from Animal Models. Am J Physiol Lung Cell Mol Physiol, 294(4): L612–631. Tu X, Donovan C, Kim RY, et al, 2021, Asthma-COPD Overlap: Current Understanding and the Utility of Experimental Models. Eur Respir Rev, 30(159): 190185. To T, Zhu J, Larsen K, et al, 2016, Progression from Asthma to Chronic Obstructive Pulmonary Disease. Is Air Pollution a Risk Factor? Am J Respir Crit Care Med, 194(4): 429–438. Strzelak A, Ratajczak A, Adamiec A, et al, 2018, 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(5): 1033. Jang A-S, Park J-S, Lee J-H, et al, 2009, The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics. J Korean Med Sci, 24(2): 209–214. Panda SK, Colonna M, 2019, Innate Lymphoid Cells in Mucosal Immunity. Front Immunol, 10:861. Kim M, Gu B, Madison MC, et al, 2019, Cigarette Smoke Induces Intestinal Inflammation via a Th17 CellNeutrophil Axis. Front mmunol, 10:75. Shikhagaie MM, Björklund ÅK, Mjösberg J, et al, 2017, Neuropilin-1 is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates. Cell Rep, 18(7): 1761–1773. Blomme EE, Provoost S, De Smet EG, et al, 2021, Quantification and Role of Innate Lymphoid Cell Subsets in Chronic Obstructive Pulmonary Disease. Clin Transl Immunology, 10(6): e1287. Silver JS, Kearley J, Copenhaver AM, et al, 2016, Inflammatory Triggers Associated with Exacerbations of COPD Orchestrate Plasticity of Group 2 Innate Lymphoid Cells in the Lungs. Nat Immunol, 17(6): 626–635. Hussell T, Bell TJ, 2014, Alveolar Macrophages: Plasticity in a Tissue-Specific Context. Nat Rev Immunol, 14(2): 81–93. Oriss TB, Raundhal M, Morse C, et al, 2017, IRF5 Distinguishes Severe Asthma in Humans and Drives Th1 Phenotype and Airway Hyperreactivity in Mice. JCI Insight, 2(10): e91019. Liu T, Baek HA, Yu H, et al, 2011, FIZZ2/RELM-β Induction and Role in Pulmonary Fibrosis. J Immunol, 187(1): 450–461. Conrad ML, Yildirim AO, Sonar SS, et al, 2009, Comparison of Adjuvant and Adjuvant-Free Murine Experimental Asthma Models. Clin Exp Allergy, 39(8): 1246–1254.