IL-17 eliminates the therapeutic effects of myelin basic protein-induced nasal tolerance in experimental autoimmune encephalomyelitis by activating IL-6.
Interleukin (IL)-17 is a proinflammatory cytokine primarily secreted by Th17 cells, which are a CD4(+) T-cell subset. Th17 cells and IL-17 are important in the pathogenesis of multiple sclerosis and in its established animal model, experimental autoimmune encephalomyelitis (EAE). However, it is unclear whether IL-17 contributes to EAE immune tolerance. We used the myelin basic protein (MBP) peptide MBP 68-86 to induce nasal tolerance to EAE, and simultaneously interfered with the tolerance by treatment with different doses of IL-17. We found that IL-17 dramatically interfered with MBP 68-86-induced immune tolerance. IL-17 administration increased IL-6 release, skewing T cell differentiation towards Th17 cells and decreasing the number of Treg cells. This led to an imbalance between Treg cells and Th17 cells and spurred the development of EAE.
Wang
G-Y
GY
Department of Neurobiology, Harbin Medical University Provincial Key Lad of Neurobiology, Harbin, Heilongjiang, China.
Sun
B
B
Kong
Q-F
QF
Zhang
Y
Y
Li
R
R
Wang
J-H
JH
Wang
D-D
DD
Lv
G X
GX
Li
H-L
HL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D004676:Myelin Basic Protein / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
C515934:Il17a protein, rat; D020381:Interleukin-17; D015850:Interleukin-6; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C110235:myelin basic protein 68-86