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

• Published in: Inflammatory bowel diseases 2014-05, Vol.20 (5), p.790-799
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation; Cytokines - genetics; Cytokines - metabolism; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Flow Cytometry; Indomethacin - toxicity; Interleukin-10 - physiology; Intestinal Diseases - chemically induced; Intestinal Diseases - immunology; Intestinal Diseases - prevention & control; Intestine, Small - drug effects; Intestine, Small - immunology; Intestine, Small - pathology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Peyer's Patches - immunology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Spleen - cytology; Spleen - immunology; Spleen - metabolism
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/MIB.0000000000000017

Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. 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. 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. 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.