4.6 Article

Macrophages and Dendritic Cells Emerge in the Liver during Intestinal Inflammation and Predispose the Liver to Inflammation

期刊

PLOS ONE
卷 9, 期 1, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0084619

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资金

  1. Japanese Ministry of Education, Culture, Sports, Science and Technology [21390233, 22021038]
  2. Japanese Ministry of Health, Labour and Welfare [22790667]
  3. Japanese MIKAMI ET AL Ministry of Health, Labour and Welfare
  4. Grants-in-Aid for Scientific Research [21390233, 24689036, 24112523, 23590949, 22021038, 24659375, 25670372, 22790667] Funding Source: KAKEN

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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(+)CD45RB(high) T cells; and IL-10(-/-) mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b(-) CD11c(low)PDCA-1(+) plasmacytoid dendritic cells (DCs) abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4(+)CD45RB(high) T cell-transferred RAG-2(-/-) mice and IL-10(-/-) mice in parallel with the emergence of macrophages (MQs) and conventional DCs (cDCs). Furthermore, liver MQ/cDCs emerging during intestinal inflammation not only promote the proliferation of naive CD4(+) T cells, but also instruct them to differentiate into IFN-gamma-producing Th1 cells in vitro. The emergence of pathological M phi/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 MQ/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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