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Monocyte-derived KCs (MoKCs) contribute to the KC pool in NASH

Cellular & Molecular Immunology volume 18, pages 518–519 (2021)Cite this article

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Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common liver disease worldwide and has increasingly become a serious hazard to human health. NAFLD consists of a spectrum of disease states ranging from simple steatosis to more severe disease termed nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatocellular carcinoma.1 In the United States, the number of NAFLD cases is projected to expand from 83.1 million in 2015 to 100.9 million in 2030, and the proportion of NASH will rise from 20 to 27% of adults with NAFLD during this interval.2 Currently, there is no effective treatment for NASH, and liver transplantation is often the only option. Thus, further research is required to understand NASH pathogenesis and to design new therapeutic strategies. Macrophages are believed to play an essential inflammatory role in NASH.3 Kupffer cells (KCs), liver-resident macrophages that self-renew by proliferation independent of monocytes, are essential to preserve tissue homeostasis. Interestingly, embryo-derived KCs (EmKCs) can be replaced by monocyte-derived KCs (MoKCs) under certain circumstances, such as Listeria monocytogenes infection.4,5 Whether KC maintenance is impaired during pathological processes such as NASH remains ill defined. In their latest publication in Immunity, Tran et al. highlight that EmKC self-renewal is impaired during NASH, leading to MoKC contributions to the KC pool. Moreover, MoKCs are maintained for a long time after NASH regression, exhibiting more inflammatory traits and abnormal responses to lipid overload.6

KCs are derived from the yolk sac and are finally located in hepatic sinusoids. KCs are a critical component of the mononuclear phagocytic system and are central to both the hepatic and systemic responses to pathogens. Moreover, KCs are emerging as critical mediators involved in both liver injury and repair.7 Depletion of monocytes and macrophages exactly attenuates the progression of NASH in animal models.8 Hepatic macrophages, specifically KCs, are believed to play crucial roles in NASH pathogenesis. However, KC biology in NASH remains poorly investigated. The relationship between inflammatory monocyte-derived macrophages (MoDMacs) and KCs is still unknown. An effective strategy to discriminate KCs from MoDMacs needs to be clarified.

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References

  1. Remmerie, A. et al. Immunity 53, 641–657 (2020).

    Article  Google Scholar 

  2. Friedman, S. L. et al. Nat. Med. 24, 908–922 (2018).

    Article  CAS  Google Scholar 

  3. Krenkel, O. & Tacke, F. Nat. Rev. Immunol. 17, 306–321 (2017).

    Article  CAS  Google Scholar 

  4. Blériot, C. et al. Immunity 42, 145–158 (2015).

    Article  Google Scholar 

  5. Theurl, I. et al. Nat. Med. 22, 945–951 (2016).

    Article  CAS  Google Scholar 

  6. Tran, S. et al. Immunity 53, 627–640 (2020).

    Article  Google Scholar 

  7. Dixon, L. J., Barnes, M., Tang, H., Pritchard, M. T. & Nagy, L. E. Compr. Physiol. 3, 785–797 (2013).

    PubMed  PubMed Central  Google Scholar 

  8. Reid, D. T. et al. PLoS ONE 11, e0159524 (2016).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Infection and Immunity, and Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China

    Yingchun Wang & Lifen Gao

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  1. Yingchun Wang
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  2. Lifen Gao
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Correspondence to Lifen Gao.

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Wang, Y., Gao, L. Monocyte-derived KCs (MoKCs) contribute to the KC pool in NASH. Cell Mol Immunol 18, 518–519 (2021). https://doi.org/10.1038/s41423-020-00606-3

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