MyD88-dependent interleukin-10 production from regulatory CD11b+Gr-1high cells suppresses development of acute cerulein pancreatitis in mice

Yuji Koike, Takanori Kanai, Keita Saeki, Yuji Nakamura, Masaru Nakano, Yohei Mikami, Yoshiyuki Yamagishi, Nobuhiro Nakamoto, Hirotoshi Ebinuma, Toshifumi Hibi

Research output: Contribution to journalArticle

7 Citations (Scopus)


We explored the role of the MyD88 signaling pathway. This pathway mediates the recognition of pathogen-associated molecular patterns and damage-associated molecular patterns via Toll-like receptors (TLRs) and/or IL-1/IL-18 via each cytokine receptor in a murine model of acute pancreatitis induced by cerulein administration. Our analysis revealed that: various TLRs and MyD88 molecules were constitutively expressed in the pancreas of cerulein-treated and untreated wild-type (WT) mice. MyD88-/- mice administered cerulein developed severe pancreatitis as compared with MyD88+/+ WT mice. The number of IL-10-expressing CD11b+Gr-1high cells in cerulein-administered MyD88-/- mice was significantly decreased. This was in accordance with a reciprocal increase in the infiltration of CD4+ T cells as compared with that in control MyD88+/+ mice. WT mice pretreated with antibiotics and administered cerulein developed milder pancreatitis as compared with control cerulein-administered mice without antibiotic treatment. The MyD88 signaling pathway contributes to the induction of regulatory IL-10-producing macrophages/myeloid-derived suppressor cells, possibly in response to non-bacterial components in the damaged pancreas. These results provide a new concept for therapeutic strategies against acute pancreatitis.

Original languageEnglish
Pages (from-to)172-177
Number of pages6
JournalImmunology Letters
Issue number2
Publication statusPublished - 2012 Dec 7



  • Cerulein
  • IL-10
  • Macrophage
  • MyD88
  • Pancreatitis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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