The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination
Year: 2018
Type: article
Abstract: Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)–γ; some Th1 cells can also be antiinflammatory through producing IL-10. 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-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo. Bhlhe40-mediated IFN-γ 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.
DOI: 10.1084/jem.20170155
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rockefeller University, Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Center for Excellence in Molecular Cell Science, State Key Laboratory of Cell Biology, National Heart, Lung, and Blood Institute
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Natural Science Foundation of China, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, NHLBI Division of Intramural Research
OpenAlex ID: W2804116873