Invariant natural killer T cells drive hepatic homeostasis in nonalcoholic fatty liver disease via sustained IL-10 expression in CD170+ Kupffer cells.
Eur J Immunol
; 53(11): e2350474, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37489253
ABSTRACT
Kupffer cells (KCs) are liver-resident macrophages involved in hepatic inflammatory responses, including nonalcoholic fatty liver disease (NAFLD) development. However, the contribution of KC subsets to liver inflammation remains unclear. Here, using high-dimensional single-cell RNA sequencing, we characterized murine embryo-derived KCs and identified two KC populations with different gene expression profiles KC-1 and KC-2. KC-1 expressed CD170, exhibiting immunoreactivity and immune-regulatory abilities, while KC-2 highly expressed lipid metabolism-associated genes. In a high-fat diet-induced NAFLD model, KC-1 cells differentiated into pro-inflammatory phenotypes and initiated more frequent communications with invariant natural killer T (iNKT) cells. In KC-1, interleukin (IL)-10 expression was unaffected by the high-fat diet but impaired by iNKT cell ablation and upregulated by iNKT cell adoptive transfer in vivo. Moreover, in a cellular co-culture system, primary hepatic iNKT cells promoted IL-10 expression in RAW264.7 and primary KC-1 cells. CD206 signal blocking in KC-1 or CD206 knockdown in RAW264.7 cells significantly reduced IL-10 expression. In conclusion, we identified two embryo-derived KC subpopulations with distinct transcriptional profiles. The CD206-mediated crosstalk between iNKT and KC-1 cells maintains IL-10 expression in KC-1 cells, affecting hepatic immune balance. Therefore, KC-based therapeutic strategies must consider cellular heterogeneity and the local immune microenvironment for enhanced specificity and efficiency.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células T Matadoras Naturais
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Hepatopatia Gordurosa não Alcoólica
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China