Tohoku J. Exp. Med., 2012, 227(1)

Paneth Cells Regulate Both Chemotaxis of Immature Dendritic Cells and Cytokine Production from Epithelial Cells

TAKAHIRO ITO,¹ HIROKI TANABE,¹ TOKIYOSHI AYABE,² CHISATO ISHIKAWA,¹ YUHEI INABA,¹ ATSUO MAEMOTO,³ TORU KONO,⁴ TOSHIFUMI ASHIDA,³ MIKIHIRO FUJIYA¹ and YUTAKA KOHGO¹

¹Division of Gastroenterology and Hematology/Oncology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan
²Innate Immunity Laboratory, Department of Cellular Life Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan
³IBD center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
⁴Division of Gastroenterologic and General Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Japan

Paneth cells in the small intestine are able to sense luminal bacteria and secrete granules that contain antibacterial peptides. Human defensin (HD)-5 and -6 are antimicrobial peptides found in human Paneth cell granules, and are major bactericidal components. We investigated whether any constituents in the Paneth cell secretions showed chemotactic activity or stimulated cytokine secretion from intestinal epithelial cells, and assessed to what extent HD-5 and -6 were responsible for these activities. The secretions from human Paneth cells and recombinant HD-5 and -6 were evaluated to elucidate their effects on the chemotaxis of dendritic cells (DCs) in a migration assay. The Paneth cell secretions were chemotactic for immature DCs at concentrations ranging from 10 to 1,000 μg/ml. HD-6 was active at 100 ng/ml, but HD-5 was not. Next, the stimulation of cytokine production by the T84 intestinal cell line was assessed using ELISA and/or an antibody array. The secretions more strongly stimulated interleukin (IL)-8 production than did the defensin peptides, and induced production of various cytokines by the antibody array. The secretions were also analyzed by high performance liquid chromatography (HPLC) and mass spectrometry (MS) in order to determine the components. A large number of molecules was found in the secretions, and HD-5 was identified as an immature propeptide. In conclusion, some constituents other than defensin in human Paneth cell secretions activated the migration of DCs and induced the production of inflammatory cytokines. Therefore, Paneth cells may play a role in the innate immunity associated with adaptive immune responses.

keywords —— chemotaxis; cytokine; dendritic cell; innate immunity; Paneth cell

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 227, 39-48

Correspondence: Takahiro Ito, Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka-higashi, Asahikawa, Hokkaido 078-8510, Japan.

e-mail: dr-ito@asahikawa-med.ac.jp