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Theranostics 2021; 11(5):2149-2169. doi:10.7150/thno.51369 This issue Cite

Research Paper

Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis

Haitao Wang1✉, Longjun Li1, Yinling Li1, Yue Li1, Yeqin Sha1, Shuang Wen1, Qiang You2, Lixin Liu3, Meiqing Shi4, Hong Zhou1✉

1. Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
2. Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
3. Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
4. Division of Immunology, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.

✉ Corresponding authors: Haitao Wang, E-mail: 807420125com; Hong Zhou, E-mail: hzhouedu.cn.

Citation:
Wang H, Li L, Li Y, Li Y, Sha Y, Wen S, You Q, Liu L, Shi M, Zhou H. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics 2021; 11(5):2149-2169. doi:10.7150/thno.51369. https://www.thno.org/v11p2149.htm
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Abstract

Graphic abstract

Rationale: Invariant natural killer T (iNKT) cells and Kupffer cells represent major hepatic populations of innate immune cells. However, their roles in steatohepatitis remain poorly understood. To elucidate their functions in steatohepatitis development, real-time, in vivo analysis is necessary to understand the pathophysiological events in the dynamic interactions between them during diet-induced steatohepatitis.

Methods: We used a steatohepatitis animal model induced by a methionine-choline-deficient (MCD) diet. Multi-photon confocal live imaging and conventional experimental techniques were employed to investigate the hepatic pathological microenvironment of iNKT and Kupffer cells, interactions between them, and the biological effects of these interactions in steatohepatitis.

Results: We found that iNKT cells were recruited and aggregated into small clusters and interacted dynamically with Kupffer cells in the early stage of steatohepatitis. Most significantly, the iNKT cells in the cluster cleared free lipids released by necrotic hepatocytes and presented a non-classical activation state with high IFN-γ expression. Furthermore, the Kupffer cells in the cell cluster were polarized to type M1. The transcriptome sequencing of iNKT cells showed upregulation of genes related to phagocytosis and lipid processing. Adoptive transfer of iNKT cells to Jα18-/- mice showed that iNKT and Kupffer cell clusters were essential for balancing the liver and peripheral lipid levels and inhibiting liver fibrosis development.

Conclusions: Our study identified an essential role for dynamic interactions between iNKT cells and Kupffer cells in promoting lipid phagocytosis and clearance by iNKT cells during early liver steatohepatitis. Therefore, modulating iNKT cells is a potential therapeutic strategy for early steatohepatitis.

Keywords: iNKT cells, Kupffer cells, steatohepatitis, phagocytosis, intravital imaging

Citation styles

APA
Wang, H., Li, L., Li, Y., Li, Y., Sha, Y., Wen, S., You, Q., Liu, L., Shi, M., Zhou, H. (2021). Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics, 11(5), 2149-2169. https://doi.org/10.7150/thno.51369.

ACS
Wang, H.; Li, L.; Li, Y.; Li, Y.; Sha, Y.; Wen, S.; You, Q.; Liu, L.; Shi, M.; Zhou, H. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics 2021, 11 (5), 2149-2169. DOI: 10.7150/thno.51369.

NLM
Wang H, Li L, Li Y, Li Y, Sha Y, Wen S, You Q, Liu L, Shi M, Zhou H. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics 2021; 11(5):2149-2169. doi:10.7150/thno.51369. https://www.thno.org/v11p2149.htm

CSE
Wang H, Li L, Li Y, Li Y, Sha Y, Wen S, You Q, Liu L, Shi M, Zhou H. 2021. Intravital imaging of interactions between iNKT and kupffer cells to clear free lipids during steatohepatitis. Theranostics. 11(5):2149-2169.

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