TY - JOUR
T1 - Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by decreasing the effector T cell population
AU - Li, Hongmei
AU - Nourbakhsh, Bardia
AU - Ciric, Bogoljub
AU - Zhang, Guang Xian
AU - Rostami, Abdolmohamad
PY - 2010/10/1
Y1 - 2010/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957230475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957230475&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1000986
DO - 10.4049/jimmunol.1000986
M3 - Article
C2 - 20805418
AN - SCOPUS:77957230475
SN - 0022-1767
VL - 185
SP - 4095
EP - 4100
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -