{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T15:14:41Z","timestamp":1793459681467,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013induced 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\u2013induced 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\u2013induced 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\u2013deficient mice lacking the IL-27 receptor. Taken together, these findings indicate that R848 stimulates IL-33\u2013induced 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.<\/jats:p>","DOI":"10.1165\/rcmb.2021-0042oc","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T13:19:55Z","timestamp":1621343995000},"page":"309-318","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":26,"title":["TLR7 Agonist Suppresses Group 2 Innate Lymphoid Cell\u2013mediated Inflammation via IL-27\u2013Producing Interstitial Macrophages"],"prefix":"10.1093","volume":"65","author":[{"given":"Shinichi","family":"Okuzumi","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, 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