Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE.
IFN-beta is anticipated to have an important function in mucosal tolerance, as it is one of the major cytokines produced by plasmacytoid dendritic cells, and has recently been suggested as central to the maintenance of mucosal homeostasis. Here, we have investigated whether oral tolerance is dependent on endogenous IFN-beta by feeding low-dose self-antigen myelin basic protein to IFN-beta(-/-) mice with subsequent induction of experimental autoimmune encephalomyelitis (EAE). Our study shows that oral tolerance was readily induced in IFN-beta(-/-) mice compared with their wild-type littermates (IFN-beta(+/+)). The non-self-antigen ovalbumin induced oral tolerance in both groups. These data indicate that endogenous IFN-beta is not required for induction of oral tolerance, whereas delivery of recombinant IFN-beta results in significant reduction in clinical score of EAE. Oral tolerance induction was associated with lower production of antigen-specific IFN-gamma, no shift toward antigen-specific Th2, Th17 or TGF-beta response was observed. Oral tolerance in IFN-beta(-/-) mice was also associated with the induction of regulatory and memory T cells in the mucosal-associated immune organs, however this was not a prerequisite for establishment of oral tolerance.
Liu
Yawei
Y
Neuroinflammation Unit, Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
Teige
Ingrid
I
Ericsson
Ida
I
Navikas
Vaidrius
V
Issazadeh-Navikas
Shohreh
S
D000284:Administration, Oral; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D047093:Eosinophil Major Basic Protein / Q000276:immunology* / Q000494:pharmacology; D007108:Immune Tolerance; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D011994:Recombinant Proteins; D016899:Interferon-beta; D047093:Eosinophil Major Basic Protein