{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:28:29Z","timestamp":1790155709726,"version":"4.0.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD4+ Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-\u03b3 and IL-17 double-producing CD4+ Th cells, termed Th17\/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17\/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17\/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1\u03b2 induces Th17\/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes. In the spleens of infected wild-type mice, Th17\/Th1 cells were induced, and expressed T-bet and Ror\u03b3t. In Pycard\u2212\/\u2212 mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17\/Th1 induction was abolished. In addition, the Fas-mediated IL-1\u03b2 production was required for Th17\/Th1 induction during bacterial infection: Th17\/Th1 induction was abolished in Fas\u2212\/\u2212 mice, whereas supplementation with recombinant IL-1\u03b2 restored Th17\/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas\u2212\/\u2212 mice infected with Listeria. IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17\/Th1 induction, indicating that IL-1\u03b2 stimulates IL-1R1 on T cells for Th17\/Th1 induction. These results indicate that IL-1\u03b2, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17\/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17\/Th1 induction during pathogenic microbial infections in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.1601373","type":"journal-article","created":{"date-parts":[[2017,7,4]],"date-time":"2017-07-04T00:30:31Z","timestamp":1499128231000},"page":"1122-1130","source":"Crossref","is-referenced-by-count":40,"title":["Inflammasome and Fas-Mediated IL-1\u03b2 Contributes to Th17\/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo"],"prefix":"10.1093","volume":"199","author":[{"given":"Ryosuke","family":"Uchiyama","sequence":"first","affiliation":[{"name":"Department of Microbiology, Hyogo College of Medicine , Nishinomiya, Hyogo 663-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Yonehara","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Graduate School of Biostudies, Kyoto University , Kyoto 606-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3245-6670","authenticated-orcid":false,"given":"Shun\u2019ichiro","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, Shinshu University Graduate School of Medicine , Matsumoto, Nagano 390-8621,","place":["Japan"]},{"name":"Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine , Matsumoto, Nagano 390-8621,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishido","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hyogo College of Medicine , Nishinomiya, Hyogo 663-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-3872","authenticated-orcid":false,"given":"Ken J","family":"Ishii","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccine Science, World Premier International Immunology Frontier Research Center, Osaka University , Suita 565-0871,","place":["Japan"]},{"name":"Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition , Osaka 567-0085,","place":["Japan"]},{"name":"Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition , Osaka 567-0085,","place":["Japan"]},{"name":"Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition , Osaka 567-0085,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7928-4875","authenticated-orcid":false,"given":"Hiroko","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hyogo College of Medicine , Nishinomiya, Hyogo 663-8501,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025030614211677400_r1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nri2295","article-title":"TH17 cells in development: an updated view of their molecular identity and genetic programming","volume":"8","author":"Dong","year":"2008","journal-title":"Nat. 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