Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by decreasing the effector T cell population.
Multiple sclerosis is a CD4(+) T cell-mediated autoimmune disease affecting the CNS. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought to be Th1-mediated diseases. However, recent studies provide strong evidence that the major pathogenic T cell subsets in EAE are Th17 cells. IL-9, a hematopoietic growth factor, is considered to be a mediator of Th17 cells, but the precise mechanisms of its action are largely unknown. The present study was designed to investigate the role of IL-9 in autoimmune demyelination. IL-9 blockade with anti-IL-9 mAb inhibited the development of EAE, reduced the serum levels of IL-17, the CNS mRNA expression of IL-17, IL-6, IFN-γ, and TNF-α, and the myelin oligodendrocyte glycoprotein (MOG)-induced IL-17, IFN-γ secretion of lymphocytes. Furthermore, anti-IL-9 mAb in culture suppressed IL-17 production of MOG-reactive T cells and their potency in adoptive transfer EAE. These findings indicate that the protective effect of IL-9 blockade in EAE was likely mediated via inhibition of the development of MOG peptide-specific T cells, which in turn led to reduced infiltration of T cells into the CNS. Thus, anti-IL-9 mAb treatment may provide an effective therapeutic strategy against autoimmune diseases.
Li
Hongmei
H
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Nourbakhsh
Bardia
B
Ciric
Bogoljub
B
Zhang
Guang-Xian
GX
Rostami
Abdolmohamad
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D020381:Interleukin-17 / Q000276:immunology*; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D016906:Interleukin-9
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