IL-9 Promotes Th17 Cell Migration into the Central Nervous System via CC Chemokine Ligand-20 Produced by Astrocytes
| Autor: | Yoshifumi Sonobe, Mariko Noda, Tomohiko Akahori, Akio Suzumura, Jun Kawanokuchi, Yoichiro Iwakura, Shijie Jin, Yan Zhou, Tetsuya Mizuno |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptor complex Encephalomyelitis Autoimmune Experimental Regulatory T cell Cellular differentiation Molecular Sequence Data Immunology Biology Mice medicine Animals Immunology and Allergy Interleukin 9 Amino Acid Sequence Cells Cultured Interleukin 4 Mice Knockout Chemokine CCL20 Experimental autoimmune encephalomyelitis Interleukin-9 Brain Cell Differentiation Cell Migration Inhibition Cell migration medicine.disease Cell biology Mice Inbred C57BL Chemotaxis Leukocyte medicine.anatomical_structure Spinal Cord Astrocytes Culture Media Conditioned Th17 Cells Interleukin-4 |
| Zdroj: | The Journal of Immunology. 186:4415-4421 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1003307 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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