T helper type 1 memory cells disseminate postoperative ileus over the entire intestinal tract

Daniel R. Engel, Arne Koscielny, Sven Wehner, Juliane Maurer, Marzena Schiwon, Lars Franken, Beatrix Schumak, Andreas Limmer, Tim Sparwasser, Andreas Hirner, Percy A. Knolle, Jörg C. Kalff, Christian Kurts

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Localized abdominal surgery can lead to disruption of motility in the entire gastrointestinal tract (postoperative ileus). Intestinal macrophages produce mediators that paralyze myocytes, but it is unclear how the macrophages are activated, especially those in unmanipulated intestinal areas. Here we show that intestinal surgery activates intestinal CD103 + CD11b + dendritic cells (DCs) to produce interleukin-12 (IL-12). This promotes interferon-γ 3 (IFN-γ 3) secretion by CCR9 + memory T helper type 1 (TH1) cells which activates the macrophages. IL-12 also caused some TH1 cells to migrate from surgically manipulated sites through the bloodstream to unmanipulated intestinal areas where they induced ileus. Preventing T cell migration with the drug FTY720 or inhibition of IL-12, T-bet (T H1-specific T box transcription factor) or IFN-γ 3 prevented postoperative ileus. CCR9 + TH1 memory cells were detected in the venous blood of subjects 1 h after abdominal surgery. These findings indicate that postoperative ileus is a T H 1 immune-mediated disease and identify potential targets for disease monitoring and therapy.

Original languageEnglish
Pages (from-to)1407-1414
Number of pages8
JournalNature Medicine
Volume16
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

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