A viral PAMP double-stranded RNA induces allergen-specific Th17 cell response in the airways which is dependent on VEGF and IL-6.
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.
Choi
J-P
JP
Department of Life Science, POSTECH Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
Kim
Y-S
YS
Tae
Y-M
YM
Choi
E-J
EJ
Hong
B-S
BS
Jeon
S G
SG
Gho
Y S
YS
Zhu
Z
Z
Kim
Yoon-Keun
YK
D056704:Adaptive Immunity; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000009:adverse effects*; D012367:RNA, Viral / Q000009:adverse effects*; D012137:Respiratory System / Q000276:immunology / Q000821:virology; D037182:T-Cell Antigen Receptor Specificity / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D000485:Allergens; D015850:Interleukin-6; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D042461:Vascular Endothelial Growth Factor A; D010047:Ovalbumin; D011070:Poly I-C