Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by decreasing the effector T cell population.

Publication/Presentation Date

10-1-2010

Abstract

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.

Volume

185

Issue

7

First Page

4095

Last Page

4100

ISSN

1550-6606

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

20805418

Department(s)

Administration and Leadership

Document Type

Article

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