Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:130

Article

Lee, Hai-Chon¹  Headley, Mark B.^1,2  Loo, Yueh-Ming²  Berlin, Aaron³  Gale, Michael, Jr.²  Debley, Jason S.^4,5  Lukacs, Nicholas W.³  Ziegler, Steven F.^1,2 

[1] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA

[2] Univ Washington, Sch Med, Dept Immunol, Seattle, WA USA

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA

[4] Seattle Childrens Res Inst, Ctr Tissue & Cell Sci, Seattle, WA USA

[5] Univ Washington, Sch Med, Dept Pediat, Div Pulm Med, Seattle, WA 98195 USA

关键词: TSLP;    RSV;    asthma;    epithelium;    T(H)2;   

DOI  :  10.1016/j.jaci.2012.07.031

来源: Elsevier

【 摘 要 】

Background: Respiratory viral infection, including respiratory syncytial virus (RSV) and rhinovirus, has been linked to respiratory disease in pediatric patients, including severe acute bronchiolitis and asthma exacerbation. Objective: The study examined the role of the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) in the response to RSV infection. Methods: Infection of human airway epithelial cells was used to examine TSLP induction after RSV infection. Air-liquid interface cultures from healthy children and children with asthma were also tested for TSLP production after infection. Finally, a mouse model was used to directly test the role of TSLP signaling in the response to RSV infection. Results: Infection of airway epithelial cells with RSV led to the production of TSLP via activation of an innate signaling pathway that involved retinoic acid induced gene I, interferon promoter-stimulating factor 1, and nuclear factor-kappa B. Consistent with this observation, airway epithelial cells from asthmatic children a produced significantly greater levels of TSLP after RSV infection than cells from healthy children. In mouse models, RSV-induced TSLP expression was found to be critical for the development of immunopathology. Conclusion: These findings suggest that RSV can use an innate antiviral signaling pathway to drive a potentially nonproductive immune response and has important implications for the role of TSLP in viral immune responses in general. (J Allergy Clin Immunol 2012;130:1187-96.)

【 授权许可】

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