An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment

被引:283
作者
Liang, Spencer C. [1 ]
Long, Andrew J. [1 ]
Bennett, Frann [1 ]
Whitters, Matthew J. [1 ]
Karim, Riyez [1 ]
Collins, Mary [1 ]
Goldman, Samuel J. [1 ]
Dunussi-Joannopoulos, Kyriaki [1 ]
Williams, Cara M. M. [1 ]
Wright, Jill F. [1 ]
Fouser, Lynette A. [1 ]
机构
[1] Wyeth Ayerst Res, Cambridge, MA 02140 USA
关键词
D O I
10.4049/jimmunol.179.11.7791
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-17A and IL-17F are related homodimeric proteins of the IL-17 family produced by Th17 cells. In this study, we show that mouse Th17 cells also produce an IL-17F/A heterodimeric protein. Whereas naive CD4(+) T cells differentiating toward the Th17 cell lineage expressed IL-17F/A in higher amounts than IL-17A/A homodimer and in lower amounts than IL-17F/F homodimer, differentiated Th17 cells expressed IL-17F/A in higher amounts than either homodimer. In vitro, IL-17F/A was more potent than IL-17F/F and less potent than IL-17A/A in regulating CXCL1 expression. Neutralization of IL-17F/A with an IL-17A-specific Ab, and not with an IL-17F-specific Ab, reduced the majority of IL-17F/A-induced CXCL1 expression. To study these cytokines in vivo, we established a Th17 cell adoptive transfer model characterized by increased neutrophilia in the airways. An IL-17A-specific Ab completely prevented Th17 cell-induced neutrophilia and CXCL5 expression, whereas Abs specific for IL-17F or IL-22, a cytokine also produced by Th17 cells, had no effects. Direct administration of mouse IL-17A/A or IL-17F/A, and not IL-17F/F or IL-22, into the airways significantly increased neutrophil and chemokine expression. Taken together, our data elucidate the regulation of IL-17F/A heterodimer expression by Th17 cells and demonstrate an in vivo function for this cytokine in airway neutrophilia.
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收藏
页码:7791 / 7799
页数:9
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