Neutralization of interleukin-9 ameliorates symptoms of experimental autoimmune myasthenia gravis in rats by decreasing effector T cells and altering humoral responses.
Interleukin-9 (IL-9) was initially thought to be a type 2 T helper (Th2)-associated cytokine involved in the regulation of autoimmune responses by affecting multiple cell types. However, it was recently shown that IL-9-producing CD4+ T cells represent a discrete subset of Th cells, designated Th9 cells. Although Th9 cells have been shown to be important in many diseases, their roles in myasthenia gravis (MG) are unclear. The aim of this study was to determine whether IL-9 and Th9 cells promote the progression of experimental autoimmune myasthenia gravis (EAMG). The results showed that the percentage of Th9 cells changed during the progression of EAMG, accompanied by an up-regulation of IL-9. Blocking IL-9 activity with antibodies against IL-9 inhibited EAMG-associated pathology in rats and reduced serum anti-acetylcholine receptor IgG levels. Neutralization of IL-9 altered the Th subset distribution in EAMG, reducing the number of Th1 cells and increasing the number of regulatory T cells. Administration of an anti-IL-9 antibody may represent an effective therapeutic strategy for MG-associated pathologies or other T-cell- or B-cell-mediated autoimmune diseases.
Department of Neurobiology, Provincial Key Laboratory of Neurobiology, Harbin Medical University, Heilongjiang, China.
Xiuhua
X
Yao
Qingfei
Q
Kong
Xiaoli
X
Xie
Jinghua
J
Wang
Na
N
Li
Yumei
Y
Liu
Bo
B
Sun
Ying
Y
Li
Guangyou
G
Wang
Wenjin
W
Li
Siying
S
Qu
Haijun
H
Zhao
Dandan
D
Wang
Xijun
X
Liu
Yao
Y
Zhang
Lili
L
Mu
Hulun
H
Li
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D056724:Immunity, Humoral; D016906:Interleukin-9 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D016906:Interleukin-9
B cells; T helper cells; experimental autoimmune myasthenia gravis; interleukin-9