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

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 intrahepatic 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.