Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice

Satoshi Hiyama, Hideki Iijima, Shinichiro Shinzaki, Takahiro Inoue, Eri Shiraishi, Shoichiro Kawai, Manabu Araki, Motohiko Kato, Yoshito Hayashi, Tsutomu Nishida, Hironobu Fujii, Akira Mukai, Naoko Shibata, Shintaro Sato, Hiroshi Kiyono, Kazuyoshi Gotoh, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Masahiko Tsujii & 1 others Tetsuo Takehara

Research output: Contribution to journalArticle

Abstract

Background: Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Methods: Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4+ T cells were co-cultured with CD103+ or CD103- dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103+ or CD103- DCs were injected with indomethacin. Results: The proportion of CD103+ DCs in PPs and MLNs and IL-10-expressing CD4+ T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103+ DCs in their MLNs, and lower proportion of IL-10-expressing CD4+ T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4+ T cells co-cultured with CD103+ DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103- DCs. Moreover, WT mice that received CD103+ DCs showed milder enteropathy than those that received CD103- DCs. Conclusions: PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103+ DCs and IL-10-producing CD4+ T cells in the intestine, independent of the commensal bacteria.

Original languageEnglish
Pages (from-to)790-799
Number of pages10
JournalInflammatory Bowel Diseases
Volume20
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Peyer's Patches
Dendritic Cells
Anti-Inflammatory Agents
Indomethacin
Interleukin-10
Pharmaceutical Preparations
T-Lymphocytes
Lymph Nodes
Mucous Membrane
Bacteria
Mucosal Immunity
Small Intestine
Intestines
Cytokines
Anti-Bacterial Agents

Keywords

  • Mucosal immunity
  • NSAID-induced enteropathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Hiyama, S., Iijima, H., Shinzaki, S., Inoue, T., Shiraishi, E., Kawai, S., ... Takehara, T. (2014). Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. Inflammatory Bowel Diseases, 20(5), 790-799. https://doi.org/10.1097/MIB.0000000000000017

Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. / Hiyama, Satoshi; Iijima, Hideki; Shinzaki, Shinichiro; Inoue, Takahiro; Shiraishi, Eri; Kawai, Shoichiro; Araki, Manabu; Kato, Motohiko; Hayashi, Yoshito; Nishida, Tsutomu; Fujii, Hironobu; Mukai, Akira; Shibata, Naoko; Sato, Shintaro; Kiyono, Hiroshi; Gotoh, Kazuyoshi; Motooka, Daisuke; Nakamura, Shota; Iida, Tetsuya; Tsujii, Masahiko; Takehara, Tetsuo.

In: Inflammatory Bowel Diseases, Vol. 20, No. 5, 01.01.2014, p. 790-799.

Research output: Contribution to journalArticle

Hiyama, S, Iijima, H, Shinzaki, S, Inoue, T, Shiraishi, E, Kawai, S, Araki, M, Kato, M, Hayashi, Y, Nishida, T, Fujii, H, Mukai, A, Shibata, N, Sato, S, Kiyono, H, Gotoh, K, Motooka, D, Nakamura, S, Iida, T, Tsujii, M & Takehara, T 2014, 'Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice', Inflammatory Bowel Diseases, vol. 20, no. 5, pp. 790-799. https://doi.org/10.1097/MIB.0000000000000017
Hiyama, Satoshi ; Iijima, Hideki ; Shinzaki, Shinichiro ; Inoue, Takahiro ; Shiraishi, Eri ; Kawai, Shoichiro ; Araki, Manabu ; Kato, Motohiko ; Hayashi, Yoshito ; Nishida, Tsutomu ; Fujii, Hironobu ; Mukai, Akira ; Shibata, Naoko ; Sato, Shintaro ; Kiyono, Hiroshi ; Gotoh, Kazuyoshi ; Motooka, Daisuke ; Nakamura, Shota ; Iida, Tetsuya ; Tsujii, Masahiko ; Takehara, Tetsuo. / Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. In: Inflammatory Bowel Diseases. 2014 ; Vol. 20, No. 5. pp. 790-799.
@article{c444e974993b4ab78d3e725f24846bff,
title = "Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice",
abstract = "Background: Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Methods: Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4+ T cells were co-cultured with CD103+ or CD103- dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103+ or CD103- DCs were injected with indomethacin. Results: The proportion of CD103+ DCs in PPs and MLNs and IL-10-expressing CD4+ T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103+ DCs in their MLNs, and lower proportion of IL-10-expressing CD4+ T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4+ T cells co-cultured with CD103+ DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103- DCs. Moreover, WT mice that received CD103+ DCs showed milder enteropathy than those that received CD103- DCs. Conclusions: PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103+ DCs and IL-10-producing CD4+ T cells in the intestine, independent of the commensal bacteria.",
keywords = "Mucosal immunity, NSAID-induced enteropathy",
author = "Satoshi Hiyama and Hideki Iijima and Shinichiro Shinzaki and Takahiro Inoue and Eri Shiraishi and Shoichiro Kawai and Manabu Araki and Motohiko Kato and Yoshito Hayashi and Tsutomu Nishida and Hironobu Fujii and Akira Mukai and Naoko Shibata and Shintaro Sato and Hiroshi Kiyono and Kazuyoshi Gotoh and Daisuke Motooka and Shota Nakamura and Tetsuya Iida and Masahiko Tsujii and Tetsuo Takehara",
year = "2014",
month = "1",
day = "1",
doi = "10.1097/MIB.0000000000000017",
language = "English",
volume = "20",
pages = "790--799",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice

AU - Hiyama, Satoshi

AU - Iijima, Hideki

AU - Shinzaki, Shinichiro

AU - Inoue, Takahiro

AU - Shiraishi, Eri

AU - Kawai, Shoichiro

AU - Araki, Manabu

AU - Kato, Motohiko

AU - Hayashi, Yoshito

AU - Nishida, Tsutomu

AU - Fujii, Hironobu

AU - Mukai, Akira

AU - Shibata, Naoko

AU - Sato, Shintaro

AU - Kiyono, Hiroshi

AU - Gotoh, Kazuyoshi

AU - Motooka, Daisuke

AU - Nakamura, Shota

AU - Iida, Tetsuya

AU - Tsujii, Masahiko

AU - Takehara, Tetsuo

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Methods: Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4+ T cells were co-cultured with CD103+ or CD103- dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103+ or CD103- DCs were injected with indomethacin. Results: The proportion of CD103+ DCs in PPs and MLNs and IL-10-expressing CD4+ T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103+ DCs in their MLNs, and lower proportion of IL-10-expressing CD4+ T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4+ T cells co-cultured with CD103+ DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103- DCs. Moreover, WT mice that received CD103+ DCs showed milder enteropathy than those that received CD103- DCs. Conclusions: PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103+ DCs and IL-10-producing CD4+ T cells in the intestine, independent of the commensal bacteria.

AB - Background: Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Methods: Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina propria (LP) of the small intestine were measured. WT and PP-null mice were given antibiotics before indomethacin treatment to evaluate enteropathy. Naive CD4+ T cells were co-cultured with CD103+ or CD103- dendritic cells (DCs) to analyze the interleukin (IL)-10 expression levels. Finally, WT mice adoptively transferred with CD103+ or CD103- DCs were injected with indomethacin. Results: The proportion of CD103+ DCs in PPs and MLNs and IL-10-expressing CD4+ T cells of PPs and the LP increased after indomethacin treatment. The PP-null mice showed greater indomethacin-induced enteropathy, fewer CD103+ DCs in their MLNs, and lower proportion of IL-10-expressing CD4+ T cells of their LP than WT mice, regardless of commensal bacteria. Naive splenic CD4+ T cells co-cultured with CD103+ DCs isolated from the MLNs of indomethacin-injected WT mice produced a higher amount of IL-10 compared with those co-cultured with CD103- DCs. Moreover, WT mice that received CD103+ DCs showed milder enteropathy than those that received CD103- DCs. Conclusions: PPs play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy, and this protection is associated with an increase in CD103+ DCs and IL-10-producing CD4+ T cells in the intestine, independent of the commensal bacteria.

KW - Mucosal immunity

KW - NSAID-induced enteropathy

UR - http://www.scopus.com/inward/record.url?scp=84902171827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902171827&partnerID=8YFLogxK

U2 - 10.1097/MIB.0000000000000017

DO - 10.1097/MIB.0000000000000017

M3 - Article

VL - 20

SP - 790

EP - 799

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 5

ER -