IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes

Y Zhou, Y Sonobe, T Akahori, S Jin… - The Journal of …, 2011 - journals.aai.org
Y Zhou, Y Sonobe, T Akahori, S Jin, J Kawanokuchi, M Noda, Y Iwakura, T Mizuno…
The Journal of Immunology, 2011journals.aai.org
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 …
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.
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