Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation

Yohei Mikami, Shinta Mizuno, Nobuhiro Nakamoto, Atsushi Hayashi, Tomohisa Sujino, Toshiro Sato, Nobuhiko Kamada, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Hirotoshi Ebinuma, Toshifumi Hibi, Akihiko Yoshimura, Takanori Kanai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2-/- mice adoptively transferred with CD4+CD45RBhigh T cells; and IL-10 -/- mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b-CD11clowPDCA-1+ plasmacytoid dendritic cells (DCs) abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4+CD45RBhigh T cell-transferred RAG-2-/- mice and IL-10-/- mice in parallel with the emergence of macrophages (Mφs) and conventional DCs (cDCs). Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4+ T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS)-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation.

Original languageEnglish
Article numbere84619
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - 2014 Jan 2

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Macrophages
dendritic cells
Liver
Dendritic Cells
macrophages
inflammation
Inflammation
liver
mice
sodium sulfate
T-cells
antigen-presenting cells
T-lymphocytes
inflammatory bowel disease
immunosuppression
colitis
dextran
interleukin-10
Immune Tolerance
Dextran Sulfate

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation. / Mikami, Yohei; Mizuno, Shinta; Nakamoto, Nobuhiro; Hayashi, Atsushi; Sujino, Tomohisa; Sato, Toshiro; Kamada, Nobuhiko; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Ebinuma, Hirotoshi; Hibi, Toshifumi; Yoshimura, Akihiko; Kanai, Takanori.

In: PLoS One, Vol. 9, No. 1, e84619, 02.01.2014.

Research output: Contribution to journalArticle

Mikami, Yohei ; Mizuno, Shinta ; Nakamoto, Nobuhiro ; Hayashi, Atsushi ; Sujino, Tomohisa ; Sato, Toshiro ; Kamada, Nobuhiko ; Matsuoka, Katsuyoshi ; Hisamatsu, Tadakazu ; Ebinuma, Hirotoshi ; Hibi, Toshifumi ; Yoshimura, Akihiko ; Kanai, Takanori. / Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation. In: PLoS One. 2014 ; Vol. 9, No. 1.
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AU - Sujino, Tomohisa

AU - Sato, Toshiro

AU - Kamada, Nobuhiko

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AU - Hisamatsu, Tadakazu

AU - Ebinuma, Hirotoshi

AU - Hibi, Toshifumi

AU - Yoshimura, Akihiko

AU - Kanai, Takanori

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AB - The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2-/- mice adoptively transferred with CD4+CD45RBhigh T cells; and IL-10 -/- mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b-CD11clowPDCA-1+ plasmacytoid dendritic cells (DCs) abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4+CD45RBhigh T cell-transferred RAG-2-/- mice and IL-10-/- mice in parallel with the emergence of macrophages (Mφs) and conventional DCs (cDCs). Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4+ T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS)-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation.

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