Short term high-fat diet induced liver ILC1 differentiation associated with the TLR9 activation

The health impact of dietary fat is a significant nutritional concern. However, the effects of high-fat diet on immune system particularly the liver regional immune function remains still unclear. Liver ILC1 has been recently identified as playing crucial roles in anti-viral defense, liver regeneration, and protection against acute liver injury. Here, in a mouse model, we uncovered that short term high-fat diet for 2 weeks obviously increased the frequency and number of ILC1 in liver. The production of TNF-α and expressions of TRAIL, CXCR3 and CXCR6 were also increased. Furthermore, EASY-RNAseq and ATAC-seq of liver ILC1 clarified the transcriptome characteristics and chromatin accessibility in response to short term high-fat diet, which were involved with lymphocyte differentiation. Mechanistically, we demonstrated that accumulation of liver ILC1 induced by short term high-fat diet was dependent on a TLR9-mediated differentiation through TLR9 inhibitor. Taken together, these findings shed light on the effect and underlying mechanism of short term high-fat diet on liver ILC1 differentiation and provide nutritional strategies and theoretical basis for the liver regional immune function regulation.