Signaling lymphocyte activation molecule regulates development of colitis in mice

Boaz Van Driel, Gongxian Liao, Xavier Romero, Michael S. O'Keeffe, Guoxing Wang, William A. Faubion, Scott B. Berger, Erica M. Magelky, Monika Manocha, Veronica Azcutia, Matthew Grisham, Francis W. Luscinskas, Emiko Mizoguchi, Rene De Waal Malefyt, Hans Christian Reinecker, Atul K. Bhan, Ninghai Wang, Cox Terhorst

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background & Aims: Signaling lymphocyte activation molecule (Slamf)1 is a co-stimulatory receptor on T cells and regulates cytokine production by macrophages and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages, therefore we investigated whether the receptor affects development of colitis in mice. Methods: We transferred CD45RBhi CD4+ T cells into Rag-/- or Slamf1-/- Rag-/- mice to induce colitis. We also induced colitis by injecting mice with an antibody that activates CD40. We determined the severity of enterocolitis based on disease activity index, histology scores, and levels of cytokine production, and assessed the effects of antibodies against Slamf1 on colitis induction. We quantified migration of monocytes and macrophage to inflamed tissues upon induction of colitis or thioglycollate-induced peritonitis and in response to tumor necrosis factor-α in an air-pouch model of leukocyte migration. Results: Colitis was reduced in Slamf1-/- Rag-/- mice, compared with Rag-/- mice, after transfer of CD45RBhi CD4+ T cells or administration of the CD40 agonist. The numbers of monocytes and macrophages were reduced in inflamed tissues of Slamf1 -/- Rag-/- mice, compared with Rag-/- mice, after induction of colitis and other inflammatory disorders. An antibody that inhibited Slamf1 reduced the level of enterocolitis in Rag-/- mice. Conclusions: Slamf1 contributes to the development of colitis in mice. It appears to indirectly regulate the appearance of monocytes and macrophages in inflamed intestinal tissues. Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1 might be a therapeutic target for inflammatory bowel disease.

Original languageEnglish (US)
Pages (from-to)1544-1554.e7
JournalGastroenterology
Volume143
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Immune Regulation
  • Inflammatory Bowel Disease
  • Mouse Model
  • TNF

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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