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

SC Liang, AJ Long, F Bennett, MJ Whitters… - The Journal of …, 2007 - journals.aai.org
SC Liang, AJ Long, F Bennett, MJ Whitters, R Karim, M Collins, SJ Goldman
The Journal of Immunology, 2007journals.aai.org
Abstract 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 …
Abstract
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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