IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity

Kawaguchi, Mio; Takahashi, Daisuke; Hizawa, Nobuyuki; Suzuki, Shintaro; Matsukura, Satoshi; Kokubu, Fumio; Maeda, Yukiko; Fukui, Youhei; Konno, Satoshi; Huang, Shau Ku; Nishimura, Masaharu; Adachi, Mitsuru

doi:10.1016/j.jaci.2005.12.1346

Cited by 230 publications

(223 citation statements)

References 20 publications

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“…Kawaguchi et al reported that the IL-17F 7488A/G variant, which causes a His-to-Arg substitution at amino acid 161 (H161R) variant, influences the risk of asthma (Kawaguchi et al, 2006). In this study, we found that GA genotype of IL-17F 7488A/G was significantly associated with an decreased risk for silicosis compared to AA carriers, and G allele may be a protective factor of silicosis.…”

Section: Discussionsupporting

confidence: 50%

Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People

Chen

Fan²,

Jin³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 50%

Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People

Chen

Fan²,

Jin³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…This variant has been reported to protect from asthma, an effect mediated through the inability of the uncommon variant form to activate cytokine production on target cells, thus behaving as a functional antagonist of proinflammatory wild-type IL-17F. 29 Should this occur in our setting, it would point to IL-17F as a cytokine contributing to transplantation tolerance. In this regard, it is of interest that donor IL17F rs2397084 also improved IFS in allo-SCT recipients; an interesting finding that needs nevertheless confirmation and further insights in experimental models of allo-SCT and infections.…”

Section: Discussionmentioning

confidence: 99%

“…Five genetic variants spanning the IL17A (rs2275913 and rs8193036), IL17F (rs763780 and rs2397084) and IL23R (rs11209026) genes were selected based on previously published evidence of association in case-control studies. [28][29][30] Preference was given to genetic variants presenting minor allele frequencies X5% and located in coding or promoter regions. Allelic variants were genotyped using bidirectional PCR amplification of specific alleles, as previously described.…”

Section: Genotypingmentioning

confidence: 99%

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

Carvalho

Cunha

Ianni

et al. 2010

Bone Marrow Transplant

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T helper (Th) 17 cells have emerged as important mediators in infectious and inflammatory diseases and, recently, in transplant rejection. We analyzed the associations between five common genetic variants in the IL-23/ Th17 signaling pathway, namely in IL17A, IL17F and IL23R genes, and clinical outcome in T cell-depleted allogeneic SCT (allo-SCT). In the multivariate analysis, variants in IL23R and IL17A genes were the most important prognostic factors. Thus, patient GA genotype at rs11209026 in IL23R was associated with improved overall survival (hazard ratio (HR) ¼ 0.48; P ¼ 0.028) and, in donor, with decreased risk of fungal infections (P ¼ 0.05). In contrast, patient TC and CC genotypes at rs8193036 in IL17A gene were associated with increased risk of CMV infection (HR ¼ 3.68; P ¼ 0.011) and patient acute GVHD (HR ¼ 7.08; P ¼ 0.008), respectively. These results suggest that genetic variants in the IL-23/Th17 inflammatory pathway are important prognostic factors for the clinical outcome of allo-SCT. Although validation studies are ultimately required, our results would suggest the potential usefulness of IL-23/Th17 genotyping in donor selection and patient evaluation.

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“…A study on IL-17F polymorphisms in asthmatic patients has identified a variant with a single amino acid substitution (H161R) that is associated with protection from asthma (41). This variant does not induce production of proinflammatory molecules from epithelial cells or the activation of signal transduction pathways.…”

Section: Discussionmentioning

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.

show abstract

IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity

Cited by 230 publications

References 20 publications

Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People

Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

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

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