Imbalance of NKp44+NKp46- and NKp44 -NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn's disease

Tetsuro Takayama, Nobuhiko Kamada, Hiroshi Chinen, Susumu Okamoto, Mina T. Kitazume, Jonathan Chang, Yumi Matuzaki, Sadafumi Suzuki, Akira Sugita, Kazutaka Koganei, Tadakazu Hisamatsu, Takanori Kanai, Toshifumi Hibi

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). Methods: We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined. Results: In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3 -CD56+ NK cells, NKp44+NKp46- (NKp44+) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44-NKp46+ (NKp46+) NK cells did not express CD127 or RORC and produced interferon (IFN)-γ. NKp46+ NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46+, NK cells from patients with CD were activated via IL-23 and produced IFN-γ; this activation required cell-to-cell contact. Conclusions: The balance of NKp44+/NKp46 + NK cells is disrupted in intestinal mucosa of patients with CD. NKp46+ NK cells might mediate the pathogenesis of CD by producing IFN-γ.

Original languageEnglish
JournalGastroenterology
Volume139
Issue number3
DOIs
Publication statusPublished - 2010 Sep

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Intestinal Mucosa
Crohn Disease
Natural Killer Cells
Inflammatory Bowel Diseases
Interferons
Mucous Membrane
Macrophages
Interleukin-23
Tretinoin
Ulcerative Colitis
Homeostasis
Transcription Factors
Cytokines
Inflammation

Keywords

  • Intestinal Macrophages
  • Intestinal NK Cells
  • UC

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

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Imbalance of NKp44+NKp46- and NKp44 -NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn's disease. / Takayama, Tetsuro; Kamada, Nobuhiko; Chinen, Hiroshi; Okamoto, Susumu; Kitazume, Mina T.; Chang, Jonathan; Matuzaki, Yumi; Suzuki, Sadafumi; Sugita, Akira; Koganei, Kazutaka; Hisamatsu, Tadakazu; Kanai, Takanori; Hibi, Toshifumi.

In: Gastroenterology, Vol. 139, No. 3, 09.2010.

Research output: Contribution to journalArticle

Takayama, T, Kamada, N, Chinen, H, Okamoto, S, Kitazume, MT, Chang, J, Matuzaki, Y, Suzuki, S, Sugita, A, Koganei, K, Hisamatsu, T, Kanai, T & Hibi, T 2010, 'Imbalance of NKp44+NKp46- and NKp44 -NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn's disease', Gastroenterology, vol. 139, no. 3. https://doi.org/10.1053/j.gastro.2010.05.040
Takayama, Tetsuro ; Kamada, Nobuhiko ; Chinen, Hiroshi ; Okamoto, Susumu ; Kitazume, Mina T. ; Chang, Jonathan ; Matuzaki, Yumi ; Suzuki, Sadafumi ; Sugita, Akira ; Koganei, Kazutaka ; Hisamatsu, Tadakazu ; Kanai, Takanori ; Hibi, Toshifumi. / Imbalance of NKp44+NKp46- and NKp44 -NKp46+ natural killer cells in the intestinal mucosa of patients with Crohn's disease. In: Gastroenterology. 2010 ; Vol. 139, No. 3.
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abstract = "Background & Aims: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). Methods: We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined. Results: In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3 -CD56+ NK cells, NKp44+NKp46- (NKp44+) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44-NKp46+ (NKp46+) NK cells did not express CD127 or RORC and produced interferon (IFN)-γ. NKp46+ NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46+, NK cells from patients with CD were activated via IL-23 and produced IFN-γ; this activation required cell-to-cell contact. Conclusions: The balance of NKp44+/NKp46 + NK cells is disrupted in intestinal mucosa of patients with CD. NKp46+ NK cells might mediate the pathogenesis of CD by producing IFN-γ.",
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AU - Takayama, Tetsuro

AU - Kamada, Nobuhiko

AU - Chinen, Hiroshi

AU - Okamoto, Susumu

AU - Kitazume, Mina T.

AU - Chang, Jonathan

AU - Matuzaki, Yumi

AU - Suzuki, Sadafumi

AU - Sugita, Akira

AU - Koganei, Kazutaka

AU - Hisamatsu, Tadakazu

AU - Kanai, Takanori

AU - Hibi, Toshifumi

PY - 2010/9

Y1 - 2010/9

N2 - Background & Aims: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). Methods: We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined. Results: In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3 -CD56+ NK cells, NKp44+NKp46- (NKp44+) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44-NKp46+ (NKp46+) NK cells did not express CD127 or RORC and produced interferon (IFN)-γ. NKp46+ NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46+, NK cells from patients with CD were activated via IL-23 and produced IFN-γ; this activation required cell-to-cell contact. Conclusions: The balance of NKp44+/NKp46 + NK cells is disrupted in intestinal mucosa of patients with CD. NKp46+ NK cells might mediate the pathogenesis of CD by producing IFN-γ.

AB - Background & Aims: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). Methods: We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined. Results: In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3 -CD56+ NK cells, NKp44+NKp46- (NKp44+) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44-NKp46+ (NKp46+) NK cells did not express CD127 or RORC and produced interferon (IFN)-γ. NKp46+ NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46+, NK cells from patients with CD were activated via IL-23 and produced IFN-γ; this activation required cell-to-cell contact. Conclusions: The balance of NKp44+/NKp46 + NK cells is disrupted in intestinal mucosa of patients with CD. NKp46+ NK cells might mediate the pathogenesis of CD by producing IFN-γ.

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KW - Intestinal NK Cells

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