IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes.
J Immunol
; 186(7): 4415-21, 2011 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-21346235
ABSTRACT
Newly discovered IL-9-producing helper T cells (Th9) reportedly exert both aggravating and suppressive roles on experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, it is still unclear whether Th9 is a distinct Th cell subset and how IL-9 functions in the CNS. In this study, we show that IL-9 is produced by naive CD4(+) T cells that were stimulated with anti-CD3 and anti-CD28 Abs under the conditions of Th2-, inducible regulatory T cell-, Th17-, and Th9-polarizing conditions and that IL-9 production is significantly suppressed in the absence of IL-4, suggesting that IL-4 is critical for the induction of IL-9 by each producing cell. The IL-9 receptor complex, IL-9R and IL-2Rγ, is constitutively expressed on astrocytes. IL-9 induces astrocytes to produce CCL-20 but not other chemokines, including CCL-2, CCL-3, and CXCL-2 by astrocytes. The conditioned medium of IL-9-stimulated astrocytes induces Th17 cell migration in vitro, which is cancelled by adding anti-CCL-20 neutralizing Abs. Treating with anti-IL-9 neutralizing Abs attenuates experimental autoimmune encephalomyelitis, decreases the number of infiltrating Th17 cells, and reduces CCL-20 expression in astrocytes. These results suggest that IL-9 is produced by several Th cell subsets in the presence of IL-4 and induces CCL-20 production by astrocytes to induce the migration of Th17 cells into the CNS.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medula Espinal
/
Encéfalo
/
Quimiotaxia de Leucócito
/
Astrócitos
/
Interleucina-9
/
Quimiocina CCL20
/
Células Th17
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article