Orchestrated regulation of immune inflammation with cell therapy in pediatric acute liver injury

Front Immunol. 2023 Jun 22:14:1194588. doi: 10.3389/fimmu.2023.1194588. eCollection 2023.

Abstract

Acute liver injury (ALI) in children, which commonly leads to acute liver failure (ALF) with the need for liver transplantation, is a devastating life-threatening condition. As the orchestrated regulation of immune hemostasis in the liver is essential for resolving excess inflammation and promoting liver repair in a timely manner, in this study we focused on the immune inflammation and regulation with the functional involvement of both innate and adaptive immune cells in acute liver injury progression. In the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, it was also important to incorporate insights from the immunological perspective for the hepatic involvement with SARS-CoV-2 infection, as well as the acute severe hepatitis of unknown origin in children since it was first reported in March 2022. Furthermore, molecular crosstalk between immune cells concerning the roles of damage-associated molecular patterns (DAMPs) in triggering immune responses through different signaling pathways plays an essential role in the process of liver injury. In addition, we also focused on DAMPs such as high mobility group box 1 (HMGB1) and cold-inducible RNA-binding protein (CIRP), as well as on macrophage mitochondrial DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in liver injury. Our review also highlighted novel therapeutic approaches targeting molecular and cellular crosstalk and cell-based therapy, providing a future outlook for the treatment of acute liver injury.

Keywords: acute liver injury; cell therapy; damage associated molecular patterns; inflammation; macrophages.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / therapy
  • Child
  • Hepatitis*
  • Humans
  • Inflammation
  • SARS-CoV-2

Grants and funding

This research was supported by grants from the National Nature Science Foundation of China (No. 82200728), the Doctoral Scientific Research Grant of Xi’an Children’s Hospital (No. 2021A03), and the Shaanxi Natural Science Research Program (No. 2022JM-480).