Cutting Edge: IL-17F, a Novel Cytokine Selectively Expressed in Activated T Cells and Monocytes, Regulates Angiogenesis and Endothelial Cell Cytokine Production

Starnes, Trevor; Robertson, Michael J.; Sledge, George W.; Kelich, Stephanie L.; Nakshatri, Harikrishna; Broxmeyer, Hal E.; Hromas, Robert

doi:10.4049/jimmunol.167.8.4137

Cited by 319 publications

(261 citation statements)

References 32 publications

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“…To examine if SCUBE1 could have a similar role, we tested whether SCUBE proteins, like LTBPs, are capable of binding growth factors or cytokines. Flag.SCUBE1 was co-expressed individually with PDGF-D, IL-8, or IL-17F, all of which are expressed in or have functions in EC (27,28,47,48). In our primary studies, Flag-.SCUBE1 proteins were capable of forming stable complexes with PDGF-D and IL-17F but not with IL-8 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium

Yang

Wasserman

et al. 2002

Journal of Biological Chemistry

145

175

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Vascular endothelial cells (EC) play a key role in a variety of pathophysiologic processes, such as angiogenesis, inflammation, cancer metastasis, and vascular diseases. As part of a strategy to identify all genes expressed in human EC, a full-length cDNA encoding a potential secreted protein harboring 10 epidermal growth factor (EGF)-like domains and one CUB domain at the carboxyl terminus (termed, SCUBE1 for Signal peptide-CUB-EGF-like domain containing protein 1) was identified. SCUBE1 shares homology with several protein families, including members of the fibrillin and Notch families, and the anticoagulant proteins, thrombomodulin and protein C. SCUBE1 mRNA is found in several highly vascularized tissues such as liver, kidney, lung, spleen, and brain and is selectively expressed in EC by in situ hybridization. SCUBE1 is a secreted glycoprotein that can form oligomers and manifests a stable association with the cell surface. A second gene encoding a homologue (designated SCUBE2) was also identified and is expressed in EC as well as other cell types. SCUBE2 is also a cell-surface protein and can form a heteromeric complex with SCUBE1. Both SCUBE1 and SCUBE2 are rapidly down-regulated in EC after interleukin-1␤ and tumor necrosis factor-␣ treatment in vitro and after lipopolysaccharide injection in vivo. Thus, SCUBE1 and SCUBE2 define an emerging family of human secreted proteins that are expressed in vascular endothelium and may play important roles in development, inflammation, and thrombosis.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium

Yang

Wasserman

et al. 2002

Journal of Biological Chemistry

145

175

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“…The first reported study of IL-17F activity showed that IL-17F induces TGF-␤, lymphotoxin ␤, and IL-2 from endothelial cells in vitro (20). A subsequent study demonstrated that IL-17F can also induce G-CSF and CXCL1 from primary human epithelial cells (11).…”

mentioning

confidence: 99%

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

Liang

Long²,

Bennett³

et al. 2007

The Journal of Immunology

316

252

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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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“…First cloned in 1993 from a murine cDNA library and known originally as CTLA-8 [23,24], IL-17A is a member of a family of IL-17 cytokines (IL-17A-F [25][26][27][28][29]) which are structurally homologous to each other and to a gene in the herpesvirus saimiri [23,30]. It was described initially as a product of activated and memory CD4 + T cells [23,30,30,31] but it is now known that the production of IL-17A is more ubiquitous and has been demonstrated in gd T cells [32], CD8 + memory T cells [31,33], eosinophils [34], neutrophils [31] and monocytes [35].…”

Section: Il-17mentioning

confidence: 99%

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali

Lombardi

Lechler

et al. 2007

Clinical and Experimental Immunology

655

470

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Cutting Edge: IL-17F, a Novel Cytokine Selectively Expressed in Activated T Cells and Monocytes, Regulates Angiogenesis and Endothelial Cell Cytokine Production

Cited by 319 publications

References 32 publications

Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium

Identification of a Novel Family of Cell-surface Proteins Expressed in Human Vascular Endothelium

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

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