Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-gamma) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4+ T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4(+)Th17 cells but increased numbers of CD4(+)CD8(+)FoxP3(+) regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4(+)CCR9(+) T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4(+)CCR9(+) T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103(+)CD11b(+) DCs were decreased and that the ability of these cells to upregulate CD4(+) T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103(+)CD11b(+) DC dysfunction contributes to the gut immune imbalance observed in NASH. (C) 2020 Elsevier Inc. All rights reserved.