Rapid Communication
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 28, 2008; 14(24): 3872-3878
Published online Jun 28, 2008. doi: 10.3748/wjg.14.3872
Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction
Mony Shuvy, Tiberiu Hershcovici, Cristina Lull-Noguera, Harry Wichers, Ofer Danay, Dan Levanon, Lidya Zolotarov, Yaron Ilan
Mony Shuvy, Tiberiu Hershcovici, Lidya Zolotarov, Yaron Ilan, Liver Unit, Department of Medicine, Hadassah, Hebrew University Medical Center, Jerusalem IL-91120, Israel
Cristina Lull-Noguera, Harry Wichers, Wageningen University and Research Center, Wageningen 6706 KN, The Netherlands
Cristina Lull-Noguera, Department of Animal Production and Food Science and Technology, University CEU-Cardenal Herrera, Avenida Seminario s/n, Moncada 46113, Valencia
Ofer Danay, Dan Levanon, Migal, Kiryat Shmone 11016, Israel
Author contributions: All authors were involved in designing the research and performed the research. Shuvy M and Hershcovici T contributed equally.
Correspondence to: Yaron Ilan, MD, Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, P.O.B 12000, Jerusalem IL-91120, Israel. ilan@hadassah.org.il
Telephone: +972-2-6778231
Fax: +972-2-6431021
Received: January 22, 2008
Revised: May 30, 2008
Accepted: June 6, 2008
Published online: June 28, 2008

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-γ 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-γ-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.

Keywords: Mushrooms, Colitis, Immune modulation, Shiitake, Natural killer T cell