Interplay of IL-33 and IL-35 Modulates Th2/Th17 Responses in Cigarette Smoke Exposure HDM-Induced Asthma.

Autor: Liu J; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Su B; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Tao P; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Yang X; Department of Pulmonary and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People's Republic of China., Zheng L; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Lin Y; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Zou X; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Yang H; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Wu W; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China., Zhang T; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China. zhtituli@163.com., Li H; Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou, People's Republic of China. lht791@163.com.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2024 Feb; Vol. 47 (1), pp. 173-190. Date of Electronic Publication: 2023 Sep 22.
DOI: 10.1007/s10753-023-01902-6
Abstrakt: Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4 + T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4 + Foxp + Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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