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 TsujiiTetsuo Takehara

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2014 May
Externally publishedYes


  • Mucosal immunity
  • NSAID-induced enteropathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology


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