A viral PAMP double‐stranded RNA induces allergen‐specific Th17 cell response in the airways which is dependent on VEGF and IL‐6

• Published in: Allergy (Copenhagen) 2010-10, Vol.65 (10), p.1322-1330
• Main Authors: Choi, J.‐P., Kim, Y.‐S., Tae, Y.‐M., Choi, E.‐J., Hong, B.‐S., Jeon, S. G., Gho, Y. S., Zhu, Z., Kim, Y.‐K.
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Allergens; Allergens - immunology; Animal models; Animals; Asthma; Asthma - immunology; Asthma - virology; Dose-Response Relationship, Drug; Double-stranded RNA; Helper cells; Hypersensitivity; IL‐6; Immune response; Immunity, Innate; Inflammation; Interleukin 17; Interleukin 6; Interleukin-6 - biosynthesis; Lung; Lymph nodes; Lymphocytes T; Mice; Mice, Transgenic; noneosinophilic asthma; Ovalbumin; Ovalbumin - pharmacology; Poly (I:C); Poly I-C - pharmacology; Respiratory System - immunology; Respiratory System - virology; Respiratory tract; Ribonucleic acid; RNA; RNA, Double-Stranded - adverse effects; RNA, Viral - adverse effects; Rodents; T-Cell Antigen Receptor Specificity - drug effects; T-Cell Antigen Receptor Specificity - immunology; Th17; Th17 Cells - immunology; Transgenic mice; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Vascular endothelial growth factor receptors; Viruses; virus‐associated asthma
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2010.02369.x

To cite this article: Choi J‐P, Kim Y‐S, Tae Y‐M, Choi E‐J, Hong B‐S, Jeon SG, Gho YS, Zhu Z, Kim Y‐K. A viral PAMP double‐stranded RNA induces allergen‐specific Th17 cell response in the airways which is dependent on VEGF and IL‐6. Allergy 2010; 65: 1322–1330. Background:  Innate immune response by a viral pathogen‐associated molecular pattern dsRNA modulates the subsequent development of adaptive immune responses. Although virus‐associated asthma is characterized by noneosinophilic inflammation, the role of Th17 cell response in the development of virus‐associated asthma is still unknown. Objective:  To evaluate the role of the Th17 cell response and its underlying polarizing mechanisms in the development of an experimental virus‐associated asthma. Methods:  An experimental virus‐associated asthma was created via airway sensitization with ovalbumin (OVA, 75 μg) and a low (0.1 μg) or a high (10 μg) doses of synthetic dsRNA [polyinosine–polycytidylic acid; poly(I:C)]. Transgenic (IL‐17‐, IL‐6‐deficient mice) and pharmacologic [a vascular endothelial growth factor receptor (VEGFR) inhibitor] approaches were used to evaluate the roles of Th17 cell responses. Results:  After cosensitization with OVA and low‐dose poly(I:C), but not with high‐dose poly(I:C), inflammation scores after allergen challenge were lower in IL‐17‐deficient mice than in wild‐type (WT) mice. Moreover, inflammation enhanced by low‐dose poly(I:C), but not by high‐dose poly(I:C), was impaired in IL‐6‐deficient mice; this phenotype was accompanied by the down‐regulation of IL‐17 production from T cells from both lymph nodes and lung tissues. Airway exposure of low‐dose poly(I:C) enhanced the production of VEGF and IL‐6, and the production of IL‐6 was blocked by treatment with a VEGFR inhibitor (SU5416). Moreover, the allergen‐specific Th17 cell response and subsequent inflammation in the low‐dose poly(I:C) model were impaired by the VEGFR inhibitor treatment during sensitization. Conclusions:  Airway exposure of low‐level dsRNA induces an allergen‐specific Th17 cell response, which is mainly dependent on VEGF and IL‐6.