Introduction: IL-1β plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE); a mouse model for multiple sclerosis (MS). We have previously demonstrated that IL-1RI–deficient mice are resistant to EAE. Furthermore, we have demonstrated that IL-1β and IL-23 promote innate IL-17 production from γδ T Cells, amplifying Th17 responses and autoimmunity. Developing countries with a high prevalence of parasitic infections are known to have a lower incidence of allergy and autoimmune diseases, often attributed to the induction of Th2 or regulatory T cells. However, this study aimed to examine whether helminth products could provide protection against autoimmunity by targeting IL-1 signalling.
Material and methods: C57BL/6 mice were subcutaneous injected with total extract (TE) from Fasciola hepatica or PBS 21 days and 7 days before the induction of EAE. Animals were monitored daily for clinical signs of the disease. On day 16 after EAE induction, mice were sacrificed and mononuclear cells from the brain were analysed by flow cytometry.
Results: We found that TE suppressed LPS-induced IL-1β but promoted IL-1RA production by bone marrow derived macrophages and dendritic cells, independent of IL-10. Moreover, TE suppressed IL-1β and IL-23-induced IL-17 production by γδ T cells by suppressing IL-1R1 and IL-23R expression on their surface. Treatment of mice with TE suppressed IL-1R expression and IL-17 production by γδ T cells and these mice were resistant to the induction of EAE. This was associated with a reduction in the development and migration of encephalitogenic IL-17 and IFNγ-producing CD4+ T cells into the CNS.
Conclusion: Our results suggest that parasitic products can attenuate autoimmune diseases by targeting IL-1 and its receptor, suppressing activation of γδ T cells and thereby preventing the development of pathogenic autoantigen-specific Th1 and Th17 cells.