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However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40-deficient CD4 Th1 cells produced less IFN-\u03b3 but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo. Bhlhe40-mediated IFN-\u03b3 production was independent of transcription factor T-bet regulation. Mice with conditional deletion of Bhlhe40 in T cells succumbed to Toxoplasma gondii infection, and blockade of IL-10 signaling during infection rescued these mice from death. Thus, our results demonstrate that transcription factor Bhlhe40 is a molecular switch for determining the fate of inflammatory and antiinflammatory Th1 cells.<\/jats:p>","DOI":"10.1084\/jem.20170155","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T11:35:18Z","timestamp":1526556918000},"page":"1813-1821","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination"],"prefix":"10.1084","volume":"215","author":[{"given":"Fang","family":"Yu","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suveena","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7360-1809","authenticated-orcid":true,"given":"Dragana","family":"Jankovic","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-0249","authenticated-orcid":true,"given":"Rama Krishna","family":"Gurram","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-0210","authenticated-orcid":true,"given":"Pan","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangqing","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rao","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiye","family":"Rieder","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keji","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-4745","authenticated-orcid":true,"given":"Jinfang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,5,17]]},"reference":[{"key":"2023072604172283600_bib1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1084\/jem.20061886","article-title":"CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis","volume":"204","author":"Anderson","year":"2007","journal-title":"J. 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