IL-9 is important for T-cell activation and differentiation in autoimmune inflammation of the central nervous system.

Publication/Presentation Date

8-1-2011

Abstract

Experimental autoimmune encephalomyelitis (EAE) is generally believed to be an autoimmune disease of the central nervous system (CNS) caused by myelin-specific Th1 and/or Th17 effector cells. The underlying cellular and molecular mechanisms, however, are not fully understood. Using mice deficient in IL-9 (IL-9(-/-) ), we showed that IL-9 plays a critical role in EAE. Specifically, IL-9(-/-) mice developed significantly less severe EAE than their WT counterparts following both immunization with myelin proteolipid protein (PLP)(180-199) peptide in the presence of Complete Freund's Adjuvant (CFA), and adoptive transfer of PLP(180-199) peptide-specific effector T cells from WT littermates. EAE-resistant IL-9(-/-) mice exhibited considerably fewer infiltrating immune cells in the CNS, with lower levels of IL-17 and IFN-γ expression, than their WT littermates. Further studies revealed that null mutation of the IL-9 gene resulted in significantly lower levels of PLP(180-199) peptide-specific IL-17 and IFN-γ production. Moreover, IL-9(-/-) memory/activated T cells exhibited decreased C-C chemokine receptors (CCR)2, CCR5, and CCR6 expression. Interestingly, IL-10 was significantly increased in IL-9(-/-) mice compared with WT littermates. Importantly, we found that IL-9-mediated Th17-cell differentiation triggers complex STAT signaling pathways.

Volume

41

Issue

8

First Page

2197

Last Page

2206

ISSN

1521-4141

Disciplines

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

PubMedID

21674475

Department(s)

Administration and Leadership

Document Type

Article

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