2021年9月
TLR7 agonist suppresses group 2 innate lymphoid cell–mediated inflammation via IL-27–producing interstitial macrophages
American Journal of Respiratory Cell and Molecular Biology
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- 巻
- 65
- 号
- 3
- 開始ページ
- 309
- 終了ページ
- 318
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1165/rcmb.2021-0042OC
Group 2 innate lymphoid cells (ILC2s) play an important role in the pathophysiology of asthma via the robust production of type 2 cytokines. Recent studies have demonstrated that TLR7 (Toll-like receptor 7) signaling skews toward a type 1 inflammatory response in asthma, which may lead to the development of novel treatment strategies. However, the effect of TLR7 signaling on ILC2-dependent nonallergic eosinophilic inflammation remains unclear. In this study, we investigated the effects of R848, a TLR7 agonist, in a mouse model of IL-33–induced eosinophilic airway inflammation. Intranasal administration of R848 decreased infiltration of airway eosinophils and ILC2s, mucus production in epithelial cells, and type 2 cytokine production. Flow cytometric analysis identified an increased number of interstitial macrophages (IMs) expressing a high level of TLR7 in the lung upon IL-33 stimulation. IL-33–induced IMs also expressed high levels of alternatively activated (M2)-type genes and chemokines (CCL17 and CCL24). However, R848 stimulation modified these gene expressions and elicited the production of IL-27. Coculture experiments revealed that IL-33–induced IMs directly suppressed ILC2 activation in response to R848. In addition, the inhibitory effects of R848 on ILC2-induced type 2 inflammation were defective in WSX-1–deficient mice lacking the IL-27 receptor. Taken together, these findings indicate that R848 stimulates IL-33–induced IMs to suppress ILC2-mediated type 2 airway inflammation via IL-27. These findings highlight the therapeutic potential of TLR7 agonists and/or IL-27 cascades in nonallergic asthma.
- リンク情報
- ID情報
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- DOI : 10.1165/rcmb.2021-0042OC
- ISSN : 1044-1549
- eISSN : 1535-4989
- PubMed ID : 34003734
- SCOPUS ID : 85114262912