Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice.
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.
Peron
Jean Pierre S
JP
Clinical Immunology Lab, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1730. Ed. Biomédicas IV, Cidade Universitária, CEP 05508-900, Sao Paulo, SP, Brazil.
Yang
Kayong
K
Chen
Mei-Ling
ML
Brandao
Wesley Nogueira
WN
Basso
Alexandre S
AS
Commodaro
Alessandra G
AG
Weiner
Howard L
HL
Rizzo
Luiz V
LV
D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)