Intrahepatic CD8(+) lymphocyte trapping during tolerance induction using mushroom derived formulations: a possible role for liver in tolerance induction

World J Gastroenterol. 2008 Jun 28;14(24):3872-8. doi: 10.3748/wjg.14.3872.

Abstract

Aim: To determine the immunomodulatory effect of Shiitake (a mushroom extract), we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.

Methods: Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract, while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-gamma ELISPOT assay.

Results: Administration of Shiitake resulted in marked alleviation of colitis, manifested by significant improvement in the macroscopic and microscopic scores, and by reduction in IFN-gamma-producing colonies in group A, compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL, respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8(+) lymphocyte trapping, demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction.

Conclusion: Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8(+) T lymphocyte trapping, thereby leading to alleviation of immune-mediated colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / pathology*
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colitis / pathology
  • Disease Models, Animal
  • Immune Tolerance / drug effects*
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Liver / drug effects
  • Liver / immunology*
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology*
  • Severity of Illness Index
  • Shiitake Mushrooms*
  • Trinitrobenzenesulfonic Acid

Substances

  • Plant Extracts
  • Interferon-gamma
  • Trinitrobenzenesulfonic Acid