Get access

Chitin microparticles for the control of intestinal inflammation

Authors

  • Katsuya Nagatani MD, PhD,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Sen Wang PhD,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Victoria Llado PhD,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Cindy W. Lau BS,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Molecular Pathology Unit, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    Search for more papers by this author
  • Zongxi Li MBBS,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Department of Immunology, China Medical University, Shenyang, Liaoning, China
    Search for more papers by this author
  • Atsushi Mizoguchi MD, PhD,

    1. Molecular Pathology Unit, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts
    Search for more papers by this author
  • Cathryn R. Nagler PhD,

    1. Department of Pathology, Committee on Immunology, University of Chicago, Chicago, Illinois
    Search for more papers by this author
  • Yoshimi Shibata PhD,

    1. Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida
    Search for more papers by this author
  • Hans-Christian Reinecker MD,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts
    Search for more papers by this author
  • J. Rodrigo Mora MD, PhD,

    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts
    Search for more papers by this author
  • Emiko Mizoguchi MD, PhD

    Corresponding author
    1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
    2. Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts
    • Massachusetts General Hospital, GRJ 702, 55 Fruit St., Boston, MA 02114
    Search for more papers by this author

Abstract

Background:

Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known.

Methods:

In this study chitin microparticles (CMPs) or phosphate-buffered saline (PBS) were orally administered to acute and chronic colitis models every 3 days for 6 consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, coculture study, and enteric bacterial analysis in dextran sodium sulfate (DSS)-induced colitis or T-cell receptor alpha (TCRα) knockout chronic colitis models.

Results:

Histologically, chitin-treated mice showed significantly suppressed colitis as compared with PBS-treated mice in both animal models. The production of interferon-gamma (IFN-γ) was upregulated in the mucosa of chitin-treated mice compared with control mice. The major source of IFN-γ-producing cells was CD4+ T cells. In mouse dendritic cells (DCs) we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced a 7-fold higher amount of IFN-γ in the culture supernatant after being cocultured with DCs and chitin as compared with the control. Proliferation of carboxyfluorescein succinimidyl ester (CFSE)low CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared with the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased interleukin (IL)-10-producing cells in noninflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa.

Conclusions:

CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon. (Inflamm Bowel Dis 2012;)

Ancillary