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TNF-alpha Contributes To The Development Of Asthma By Enhancing IL-23/Th17 And Th2 Immune Responses

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Authors
Lee, H.; Jeon, E.; Bang, B.; Shim, E.; Kim, T.; Lee, S.; Kim, S.; Park, H.; Kim, S.; Kim, Y.; Min, K.; Cho, S.; Chang, Y.; Kang, H.; Kim, K.; Jung, J.; Kwon, J.
Issue Date
2010-02
Publisher
MOSBY-ELSEVIER
Citation
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY; Vol.125 2; AB105-AB105
Abstract
RATIONALE: TNF-a has been postulated to be a critical mediator contributing
to airway inflammation. The purpose of this study is to evaluate
the role of TNF-a in the induction of Th17 and Th2 cells related to asthma
pathogenesis.
METHODS: Wild type and TNF-a knockout (TNF-a-/-) C57BL/6 mice
were intranasally sensitized with LPS 0.1 mg plus OVA. To see the relation
between TNF-a and associated effector cytokines, we replenished TNFa
-/- mice with IL-23 and IL-4 during sensitization period. To assess cellular
resources, CD11c+ cells isolated from lung tissue after sensitization were
treated with anti-TNF-a Ab.
RESULTS: TNF-a deficiency reduced the number of eosinophils and airway
hyperresponsiveness (AHR) in murine asthma model. TNF-a-/- mice
showed significant reduction in the level of IL-23 and IL-4 levels after sensitization
in bronchoalveolar lavage fluid as well as IL-17A, IL-4 levels in
CD4+ T cells after challenge compared withWTmice. Supplementation of
IL-23 in TNF-a-/- mice resulted in complete restoration of eosinophilic airway
inflammation, AHR, and IL-17A and IL-4 expression in CD4+ T cells.
In comparison, supplementation of IL-4 restored eosinophils infiltration in
part in the absence of TNF-a. Anti-TNF-a Ab treatment after sensitization
significantly diminished the population of IL-23p19-secreting CD11c+
cells in lung.
CONCLUSIONS: TNF-a plays an important role in the development of
airway inflammation by enhancing IL-23/Th17 and Th2 immune
responses.
ISSN
0091-6749
Language
English
URI
https://hdl.handle.net/10371/77527
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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