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

Hongmei Li, Bardia Nourbakhsh, Melissa Cullimore, Guang Xian Zhang, Abdolmohamad Rostami

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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 PLP180-199 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 PLP180-199 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.

Original languageEnglish (US)
Pages (from-to)2197-2206
Number of pages10
JournalEuropean Journal of Immunology
Volume41
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Encephalitogenic T cells
  • IL-9
  • STAT signaling pathway

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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