Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function.

Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Research Abstract Details 

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Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Abstract Text:

Airway DCs play a crucial role in the pathogenesis of allergic asthma, and interfering with their function could constitute a novel form of therapy. The sphingosine 1-phosphate receptor agonist FTY720 is an oral immunosuppressant that retains lymphocytes in lymph nodes and spleen, thus preventing lymphocyte migration to inflammatory sites. The accompanying lymphopenia could be a serious side effect that would preclude the use of FTY720 as an antiasthmatic drug. Here we show in a murine asthma model that local application of FTY720 via inhalation prior to or during ongoing allergen challenge suppresses Th2-dependent eosinophilic airway inflammation and bronchial hyperresponsiveness without causing lymphopenia and T cell retention in the lymph nodes. Effectiveness of local treatment was achieved by inhibition of the migration of lung DCs to the mediastinal lymph nodes, which in turn inhibited the formation of allergen-specific Th2 cells in lymph nodes. Also, FTY720-treated DCs were intrinsically less potent in activating naive and effector Th2 cells due to a reduced capacity to form stable interactions with T cells and thus to form an immunological synapse. These data support the concept that targeting the function of airway DCs with locally acting drugs is a powerful new strategy in the treatment of asthma.

Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Publishing Authors By Initials

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Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 116

Page Numbers: 2935-44

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 5

MONTH: Nov

YEAR: 2006

Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Information

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LANGUAGE: eng

NlmUniqueID: 7802877

Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Keywords Mesh Terms:

KEYWORDS: Sphingosine

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. Information

Substance Name: sphingosine 1-phosphate

Registry Number: 26993-30-6

Grant and Affiliation Information for Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function.

AFFILIATION: Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Country: United States

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MEDLINETA: J Clin Invest

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