Role of inflammatory macrophages and CCR9/CCL25 chemokine axis in the pathogenesis of liver injury as a therapeutic target

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Abstract

It is widely known that a variety of immune cells in the liver contribute to the pathogenesis of liver diseases. Recently, roles of chemokines/chemokines receptors axes regarding the migration of immune competent cells to the inflamed liver have been reported as possible therapeutic targets. We here showed that CCR9+ CD11b+ macrophages play an important role during the course of Concanavalin A-induced murine acute liver injury as well as human acute hepatitis via the production of inflammatory cytokines and the Th1 induction. Further analysis using liver-shielded radiation and bone marrow (BM) transplantation model mice revealed that these CCR9+ CD11b+ macrophages are originated from BM-derived monocytes, but not liver resident macrophages (Kupffer cells). Furthermore, these CD11b+ inflammatory macrophages in contact with hepatic stellate cells contribute to the pathogenesis of murine experimental liver fibrosis via CCR9/CCL25 axis. Collectively, these results with further verification in human samples clarify the pathogenic role of CCR9/CCL25 axis as therapeutic target of a variety of liver diseases.

Original languageEnglish
Pages (from-to)460-467
Number of pages8
JournalJapanese Journal of Clinical Immunology
Volume39
Issue number5
Publication statusPublished - 2016

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Chemokines
Macrophages
Liver
Wounds and Injuries
Liver Diseases
Therapeutics
Hepatic Stellate Cells
Kupffer Cells
Chemokine Receptors
Concanavalin A
Bone Marrow Transplantation
Liver Cirrhosis
Hepatitis
Monocytes
Radiation
Cytokines

Keywords

  • Acute hepatitis
  • Chemokines and chemokine receptors
  • Liver cirrhosis
  • Liver fibrosis
  • Macrophage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Role of inflammatory macrophages and CCR9/CCL25 chemokine axis in the pathogenesis of liver injury as a therapeutic target",
abstract = "It is widely known that a variety of immune cells in the liver contribute to the pathogenesis of liver diseases. Recently, roles of chemokines/chemokines receptors axes regarding the migration of immune competent cells to the inflamed liver have been reported as possible therapeutic targets. We here showed that CCR9+ CD11b+ macrophages play an important role during the course of Concanavalin A-induced murine acute liver injury as well as human acute hepatitis via the production of inflammatory cytokines and the Th1 induction. Further analysis using liver-shielded radiation and bone marrow (BM) transplantation model mice revealed that these CCR9+ CD11b+ macrophages are originated from BM-derived monocytes, but not liver resident macrophages (Kupffer cells). Furthermore, these CD11b+ inflammatory macrophages in contact with hepatic stellate cells contribute to the pathogenesis of murine experimental liver fibrosis via CCR9/CCL25 axis. Collectively, these results with further verification in human samples clarify the pathogenic role of CCR9/CCL25 axis as therapeutic target of a variety of liver diseases.",
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AB - It is widely known that a variety of immune cells in the liver contribute to the pathogenesis of liver diseases. Recently, roles of chemokines/chemokines receptors axes regarding the migration of immune competent cells to the inflamed liver have been reported as possible therapeutic targets. We here showed that CCR9+ CD11b+ macrophages play an important role during the course of Concanavalin A-induced murine acute liver injury as well as human acute hepatitis via the production of inflammatory cytokines and the Th1 induction. Further analysis using liver-shielded radiation and bone marrow (BM) transplantation model mice revealed that these CCR9+ CD11b+ macrophages are originated from BM-derived monocytes, but not liver resident macrophages (Kupffer cells). Furthermore, these CD11b+ inflammatory macrophages in contact with hepatic stellate cells contribute to the pathogenesis of murine experimental liver fibrosis via CCR9/CCL25 axis. Collectively, these results with further verification in human samples clarify the pathogenic role of CCR9/CCL25 axis as therapeutic target of a variety of liver diseases.

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