Ccl2‐Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution

Ccl2‐Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution

Abstract Inflammation is highlighted as an initial factor that helps orchestrate liver reconstitution. However, the precise mechanisms controlling inflammation during liver reconstitution have not been fully elucidated. In this study, a clear immune response is demonstrated during hepatic reconstitu...

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Main Authors: Rui Wang, Qing Liang, Qian Zhang, Shuchao Zhao, Yuxiang Lin, Bing Liu, Yinjiang Ma, Xiaoya Mai, Quanze Fu, Xiaorui Bao, Nan Wang, Binglin Chen, Peng Yan, Yongsheng Zhu, Kejia Wang
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
Subjects:
inflammatory milieu
liver reconstitution
macrophage polarization
regulatory T cell
type 1 innate lymphoid cell
Online Access:https://doi.org/10.1002/advs.202403849
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Summary:Abstract Inflammation is highlighted as an initial factor that helps orchestrate liver reconstitution. However, the precise mechanisms controlling inflammation during liver reconstitution have not been fully elucidated. In this study, a clear immune response is demonstrated during hepatic reconstitution. Inhibition of the hepatic inflammatory response retards liver regeneration. During this process, Ccl2 is primarily produced by type 1 innate lymphoid cells (ILC1s), and ILC1‐derived Ccl2 recruits peripheral ILC1s and regulatory T cells (Tregs) to the liver. Deletion of Ccl2 or Tregs exacerbates hepatic injury and inflammatory cytokine release, accelerating liver proliferation and regeneration. The adoption of Tregs and IL‐10 injection reversed these effects on hepatocyte regenerative proliferation. Additionally, Treg‐derived IL‐10 can directly induce macrophage polarization from M1 to M2, which alleviated macrophage‐secreted IL‐6 and TNF‐α and balanced the intrahepatic inflammatory milieu during liver reconstitution. This study reveals the capacity of Tregs to modulate the intrahepatic inflammatory milieu and liver reconstitution through IL‐10‐mediated macrophage polarization, providing a potential opportunity to improve hepatic inflammation and maintain homeostasis.
ISSN:2198-3844

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