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.
authors.affiliation: *Department of Gastroenterology and Hepatology, and †Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan; ‡Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan; §Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; and ¶Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hiyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Shinichiro
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authors.lastname: Shinzaki
authors.forename: Takahiro
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authors.lastname: Inoue
authors.forename: Eri
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authors.lastname: Shiraishi
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Kawai
authors.forename: Manabu
authors.initials: M
authors.lastname: Araki
authors.forename: Motohiko
authors.initials: M
authors.lastname: Kato
authors.forename: Yoshito
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authors.lastname: Hayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.forename: Akira
authors.initials: A
authors.lastname: Mukai
authors.forename: Naoko
authors.initials: N
authors.lastname: Shibata
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Gotoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Motooka
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007213:Indomethacin / Q000633:toxicity*; D016753:Interleukin-10 / Q000502:physiology; D007410:Intestinal Diseases / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D007213:Indomethacin