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Interplay of IL-33 and IL-35 Modulates Th2/Th17 Responses in Cigarette Smoke Exposure HDM-Induced Asthma.
- Source :
-
Inflammation . Feb2024, Vol. 47 Issue 1, p173-190. 18p. - Publication Year :
- 2024
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INTERLEUKIN-33
*CIGARETTE smoke
*SMOKING
*HOUSE dust mites
*T cells
Subjects
Details
- Language :
- English
- ISSN :
- 03603997
- Volume :
- 47
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 174918357
- Full Text :
- https://doi.org/10.1007/s10753-023-01902-6