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Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat T2D and exert anti-inflammatory actions through a single, well-defined GLP-1 receptor (GLP-1R). Although highly expressed in the lung, little is known about the role of the GLP-1R in the context of pulmonary inflammation. Here we examined the consequences of gain or loss of GLP-1R activity in infectious and noninfectious lung inflammation. We studied wild-type mice treated with a GLP-1R agonist, and Glp1r\u2013\/\u2013 mice, in the setting of bleomycin-induced noninfectious lung injury and influenza virus infection. Loss of the GLP-1R attenuated the severity of bleomycin-induced lung injury, whereas activation of GLP-1R signaling increased pulmonary inflammation via the sympathetic nervous system. In contrast, GLP-1R agonism reduced the pathogen load in mice with experimental influenza virus infection in association with increased expression of intracellular interferon-inducible GTPases. Notably, the GLP-1 receptor agonist liraglutide improved the survival rate after influenza virus infection. Our results reveal context-dependent roles for the GLP-1 system in the response to lung injury. Notably, the therapeutic response of GLP-1R agonism in the setting of experimental influenza virus infection may have relevance for ongoing studies of GLP-1R agonism in people with T2D susceptible to viral lung injury.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa201","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T12:21:05Z","timestamp":1604060465000},"source":"Crossref","is-referenced-by-count":31,"title":["GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice"],"prefix":"10.1210","volume":"161","author":[{"given":"Takehiro","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsunori","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Imai","sequence":"additional","affiliation":[{"name":"Laboratory of Regulation for Intractable Infectious Diseases, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation Health and Nutrition, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Drucker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Seino","sequence":"additional","affiliation":[{"name":"Kansai Electric Power Medical Research Institute, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-0815","authenticated-orcid":false,"given":"Yuichiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan"},{"name":"Kansai Electric Power Medical Research Institute, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"issue":"8","key":"2021121718183567300_CIT0001","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.tins.2019.05.005","article-title":"Neuronal regulation of immunity in the skin 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