作者
Alejandro Torres‐Hernandez,Wei Wang,Yuri E. Nikiforov,Karla Tejada,Luisana E. Torres,Aleksandr Kalabin,Salma Adam,Jingjing Wu,Lu Lu,Ruonan Chen,Aaron C. Lemmer,Jimmy Camargo,Mautin Hundeyin,Brian Diskin,Berk Aykut,Emma Kurz,Juan Andres Kochen Rossi,M. A. Q. Khan,Miguel Liria,Gustavo Sanchez,Nan Wu,Wenyu Su,Steven P. Adams,Muhammad Israr Ul Haq,Mohammad Saad Farooq,Varshini Vasudevaraja,Joshua Leinwand,George Miller
摘要
Background and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A + phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4 + , PD1 + , Ly6C + CD44 + phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4 + T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.