Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis

Nobuhiko Kamada, Tadakazu Hisamatsu, Susumu Okamoto, Hiroshi Chinen, Taku Kobayashi, Toshiro Sato, Atsushi Sakuraba, Mina T. Kitazume, Akira Sugita, Kazutaka Koganei, Kiyoko S. Akagawa, Toshifumi Hibi

Research output: Contribution to journalArticle

376 Citations (Scopus)

Abstract

Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine. This subset expressed both macrophage (CD14, CD33, CD68) and DC markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as IL-23, TNF-α, and IL-6, than typical intestinal resident macrophages (CD14 -CD33+ macrophages). In patients with Crohn disease (CD), the number of these CD14+ macrophages were significantly increased compared with normal control subjects. In addition to increased numbers of cells, these cells also produced larger amounts of IL-23 and TNF-α compared with those in normal controls or patients with ulcerative colitis. In addition, the CD14 + macrophages contributed to IFN-γ production rather than IL-17 production by lamina propria mononuclear cells (LPMCs) dependent on IL-23 and TNF-α. Furthermore, the IFN-γ produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype. Collectively, these data suggest that this IL-23/IFN-γ-positive feedback loop induced by abnormal intestinal macrophages contributes to the pathogenesis of chronic intestinal inflammation in patients with CD.

Original languageEnglish
Pages (from-to)2269-2280
Number of pages12
JournalJournal of Clinical Investigation
Volume118
Issue number6
DOIs
Publication statusPublished - 2008 Jun 2

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Interleukin-23
Crohn Disease
Macrophages
Mucous Membrane
Cytokines
Bacteria
Interleukin-17
Ulcerative Colitis
Intestines
Interleukin-6
Cell Count
Inflammation

ASJC Scopus subject areas

  • Medicine(all)

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Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. / Kamada, Nobuhiko; Hisamatsu, Tadakazu; Okamoto, Susumu; Chinen, Hiroshi; Kobayashi, Taku; Sato, Toshiro; Sakuraba, Atsushi; Kitazume, Mina T.; Sugita, Akira; Koganei, Kazutaka; Akagawa, Kiyoko S.; Hibi, Toshifumi.

In: Journal of Clinical Investigation, Vol. 118, No. 6, 02.06.2008, p. 2269-2280.

Research output: Contribution to journalArticle

Kamada, N, Hisamatsu, T, Okamoto, S, Chinen, H, Kobayashi, T, Sato, T, Sakuraba, A, Kitazume, MT, Sugita, A, Koganei, K, Akagawa, KS & Hibi, T 2008, 'Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis', Journal of Clinical Investigation, vol. 118, no. 6, pp. 2269-2280. https://doi.org/10.1172/JCI34610
Kamada, Nobuhiko ; Hisamatsu, Tadakazu ; Okamoto, Susumu ; Chinen, Hiroshi ; Kobayashi, Taku ; Sato, Toshiro ; Sakuraba, Atsushi ; Kitazume, Mina T. ; Sugita, Akira ; Koganei, Kazutaka ; Akagawa, Kiyoko S. ; Hibi, Toshifumi. / Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 6. pp. 2269-2280.
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