Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory immune response directed against myelin antigens of the central nervous system. In its murine model, EAE, Th17 cells play an important role in disease pathogenesis. These cells can induce blood-brain barrier disruption and CNS immune cells activation, due to the capacity to secrete high levels of IL-17 and IL-22 in an IL-6+TGF-β dependent manner. Thus, using the oral tolerance model, by which 200 μg of MOG 35-55 is given orally to C57BL/6 mice prior to immunization, we showed that the percentage of Th17 cells as well as IL-17 secretion is reduced both in the periphery and also in the CNS of orally tolerated animals. Altogether, our data corroborates with the pathogenic role of IL-17 and IFN-γ in EAE, as its reduction after oral tolerance, leads to an overall reduction of pro-inflammatory cytokines, such as IL-1α, IL-6, IL-9, IL-12p70 and the chemokines MIP-1β, RANTES, Eotaxin and KC in the CNS. It is noteworthy that this was associated to an increase in IL-10 levels. Thus, our data clearly show that disease suppression after oral tolerance induction, correlates with reduction in target organ inflammation, that may be caused by a reduced Th1/Th17 response.

Central Nervous System Resident Cells in Neuroinflammation: A Brave New World.

“…Thus, the findings in p19 KO mice highlighted the fact that these mice were resistant to EAE induction due to the reduced survival of encephalitogenic Th17 cells in the periphery. However, it is well accepted that both Th1 and Th17 cells are found in focal lesions in MS and EAE, comprising around 20-25% and 10-15% of the CNS infiltrating T CD4 cells respectively (Murphy AC 2010;Peron JP 2010). Moreover, it is well accepted the fact both populations intimately interact with CNS resident cells, as astrocytes, microglia and neurons.…”

Functional plasticity in human FOXP3 + regulatory T cells

“…Both have proven to be efficacious in mouse models of autoimmunity. [17][18][19][20][21] These encouraging results have made vaccines and cellular transfer therapy important avenues currently pursued in clinical trials. 22 Approaches selectively favoring the survival of Treg cells include the provision of low doses of IL-2, or the use of immunosuppressive pharmaceutical agents such as Cyclosporin A and Rapamycin, which have recently been found to selectively modulate biochemical pathways in Tconv or Treg cells.…”

Original article Effect of oral administration of pig spinal cord hydrolysate on clinical and histopathological symptoms of experimental allergic encephalomyelitis in rats

“…Our pilot trials examining the cytokine levels showed increased IL-10 levels in brain and spinal cord homogenates in rats fed with pig spinal cord hydrolysate in a dose of 20 mg/kg [20]. Peron et al [29] observed that mice with MOG35-55-induced EAE, and the same antigen given orally to induce oral tolerance, had a reduced amount of both Th17 and Th1 cells infiltrating into the CNS. Diminished perivascular infiltrations in the CNS were also observed in rats fed with MBP conjugated with the cholera toxin B subunit [36].…”