Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show that compared with WT mice, OX40-/- mice exhibit decreased liver fat accumulation, lobular inflammation, and focal necrosis after feeding with diets that induce NASH. Mechanistically, OX40 deficiency suppresses Th1 and Th17 differentiation, and OX40 deficiency in T cells inhibits monocyte migration, antigen presentation, and M1 polarization. Soluble OX40 stimulation alone upregulates antigen presentation, chemokine receptor expression, and proinflammatory cytokine secretion by liver monocytes. Furthermore, plasma soluble OX40 levels are positively associated with NASH in humans, suggesting clinical relevance of the findings. In conclusion, we show a mechanism for T cell regulation of innate immune cells. OX40 is a key regulator of both intrahepatic innate and adaptive immunity, generates two-way signals, and promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development.
Pubmed ID: 30590049 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsCommercial supplier and developer of in vivo antibodies. Provides antibodies and antibody production services.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsThis monoclonal targets FOXP3
View all literature mentionsThis monoclonal targets CD192
View all literature mentionsThis monoclonal targets CD86 (B7-2)
View all literature mentionsThis monoclonal targets CD192
View all literature mentionsThis monoclonal targets CD86 (B7-2)
View all literature mentionsThis monoclonal targets TLR4/MD-2 Complex
View all literature mentionsThis monoclonal targets CD195 (CCR5)
View all literature mentionsThis monoclonal targets MHC Class II (I-A/I-E)
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets CD134 (OX40)
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD134 (OX40)
View all literature mentionsThis monoclonal targets CD40
View all literature mentionsThis monoclonal targets TCR beta
View all literature mentionsThis monoclonal targets NK1.1
View all literature mentionsThis monoclonal targets TCR beta
View all literature mentionsThis monoclonal targets NK1.1
View all literature mentionsThis monoclonal targets NK1.1
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets TNF alpha
View all literature mentionsThis monoclonal targets IFN gamma
View all literature mentionsThis monoclonal targets CD199 (CCR9)
View all literature mentionsThis monoclonal targets CD185 (CXCR5)
View all literature mentionsThis monoclonal targets CD197 (CCR7)
View all literature mentionsThis monoclonal targets CD183 (CXCR3)
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets CD134 (OX40)
View all literature mentions