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LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis

Author

Listed:
  • Dan-Pei Li

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Li Huang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Ran-Ran Kan

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Xiao-Yu Meng

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Shu-Yun Wang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Hua-Jie Zou

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Ya-Ming Guo

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Pei-Qiong Luo

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Li-Meng Pan

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Yu-Xi Xiang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Bei-Bei Mao

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Yu-Yu Xie

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Zhi-Han Wang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Min Yang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Rui He

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Yan Yang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Zhe-Long Liu

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Jun-Hui Xie

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • De-Lin Ma

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Ben-Ping Zhang

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Shi-Ying Shao

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Xi Chen

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Si-Miao Xu

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Wen-Tao He

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Wen-Jun Li

    (Huazhong University of Science and Technology)

  • Yong Chen

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

  • Xue-Feng Yu

    (Huazhong University of Science and Technology
    Branch of National Clinical Research Center for Metabolic Diseases)

Abstract

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB−/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Suggested Citation

  • Dan-Pei Li & Li Huang & Ran-Ran Kan & Xiao-Yu Meng & Shu-Yun Wang & Hua-Jie Zou & Ya-Ming Guo & Pei-Qiong Luo & Li-Meng Pan & Yu-Xi Xiang & Bei-Bei Mao & Yu-Yu Xie & Zhi-Han Wang & Min Yang & Rui He &, 2023. "LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40183-3
    DOI: 10.1038/s41467-023-40183-3
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    References listed on IDEAS

    as
    1. Junke Zheng & Masato Umikawa & Changhao Cui & Jiyuan Li & Xiaoli Chen & Chaozheng Zhang & HoangDinh Huynh & Xunlei Kang & Robert Silvany & Xuan Wan & Jingxiao Ye & Alberto Puig Cantó & Shu-Hsia Chen &, 2012. "Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development," Nature, Nature, vol. 485(7400), pages 656-660, May.
    2. Siyu Chen & Mengyang Feng & Shiyao Zhang & Zhewen Dong & Yifan Wang & Wenxiang Zhang & Chang Liu, 2019. "Angptl8 mediates food-driven resetting of hepatic circadian clock in mice," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    3. Junke Zheng & Masato Umikawa & Changhao Cui & Jiyuan Li & Xiaoli Chen & Chaozheng Zhang & HoangDinh Huynh & Xunlei Kang & Robert Silvany & Xuan Wan & Jingxiao Ye & Alberto Puig Cantó & Shu-Hsia Chen &, 2012. "Correction: Corrigendum: Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development," Nature, Nature, vol. 488(7413), pages 684-684, August.
    4. Yu Zhang & Xian Guo & Wanyao Yan & Yan Chen & Mengxiang Ke & Cheng Cheng & Xiuqin Zhu & Weili Xue & Qiaoqiao Zhou & Ling Zheng & Shun Wang & Bin Wu & Xinran Liu & Liang Ma & Lianqi Huang & Kun Huang, 2017. "ANGPTL8 negatively regulates NF-κB activation by facilitating selective autophagic degradation of IKKγ," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    5. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
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