Effects of immune system cells in GvHD and corresponding therapeutic strategies.

Allogeneic tissue transplantation is one of the most effective treatments for several diseases and injuries, in particular, malignant and non-malignant hematological conditions. Following this procedure, transplanted tissue encounters various complications, one of the most serious being graft-versus-host disease (GvHD). The management of GvHD directly affects the success of transplantation and the survival rate of the patient; therefore, many studies have focused on GvHD prevention and control. This review briefly explains the transplantation process, causes of graft rejection, and importance of the human leukocyte antigen system. Initially, we address the pathophysiology and immunobiology of GvHD, the cells involved in this complication, the differences between chronic and acute GvHD, and the importance of graft-versus-leukemia. Interestingly, various types of immune cells are involved in GvHD pathogenesis. After explaining how these cells affect the GvHD process, we discuss the studies conducted to control and reduce GvHD symptoms.

Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses.

Multiple Sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies for MS. Therefore, we investigated the efficacy of oral administration of a Myelin Oligodendrocyte Glycoprotein (MOG) in the treatment of EAE. Female C57BL/6 mice were utilized in three groups (Control group, received PBS orally; prevention group, oral administration of MOG35-55 two weeks before EAE induction; treatment group, oral administration of MOG35-55 after EAE induction). MOG administration, both as prevention and treatment, significantly controlled clinical score, weight loss, CNS inflammation, and demyelination, mainly through the modulation of T cell proliferation, and reduction in pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-γ, IL-17, T-bet, and ROR-γt. MOG administration, both as prevention and treatment, also induced anti-inflammatory cytokines and transcription factors, including IL-4, TGF-ß, GATA-3, and Foxp3. The results showed that oral administration of MOG, both as prevention and treatment, could efficiently control EAE development. Immunomodulatory mechanisms include the induction of Th2 and Treg cells and the suppression of pro-inflammatory Th1 and Th17 cells.

Daphnetin alleviates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating Th2 and regulatory T cells.

Multiple sclerosis (MS) is the most typical chronic inflammatory, autoimmune demyelinating disease of the central nervous system (CNS) which leads to physical dysfunction and paralysis in patients. A commonly used animal model for this disease is experimental autoimmune encephalomyelitis (EAE). Daphnetin (7,8­dihydroxycoumarin) has been reported to exert various pharmacological activities, such as being neuroprotective and anti­inflammatory, together with having antioxidant, anticancer, and antiviral properties. Eight­week­old C57BL/6 female mice were segregated into 3 groups, namely 1) a control group receiving PBS, 2) a low­dose treatment group receiving 2 mg/kg of daphnetin, and, 3) a high­dose treatment group receiving 8 mg/kg of daphnetin. EAE was induced with a subcutaneous injection of a combination of myelin oligodendrocyte glycoprotein (MOG) and complete Freund's adjuvant. On the day of induction, and again two days later, mice were injected intraperitoneally with pertussis toxin. Histological studies showed low lymphocyte infiltration and demyelination in the high and low dose treated groups. The ratio of spleen Treg cells and the levels of IL­4, IL­10, TGF­ß, and IL­33 enhanced significantly in the treatment group related to the control group. Furthermore, both IL­27 and IL­35 were also enhanced significantly in the treatment group compared to the control group. Moreover, the levels of IFN­Î³, TNF­α, and IL­17 displayed a noticeable reduction in the daphnetin treated group. Daphnetin appears to improve the disease by increasing the expression of anti­inflammatory cytokines and transcription factors (IL­4, IL­10, IL­33, GATA3, TGF­ß, FoxP3), and reducing the production of pro­inflammatory cytokines and transcription factors (IFN­Î³, STAT4, T­bet, IL­17, STAT3, ROR­Î³t, TNF­α).