Blocking OX40L Function Inhibits TSLP-Induced Atopic Disease In Lung And Skin (37.11)

Autor: Dhaya Seshasayee, Meijuan Zhou, Jean Shu, Eric Suto, Juan Zhang, Wyne Pun Lee, Stefan Seeber, Maria Fuentes, Sarah Hymowitz, Flavius Martin
Rok vydání: 2007
Předmět:
Zdroj: The Journal of Immunology. 178:S20-S20
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.178.supp.37.11
Popis: OX40L-OX40 interactions have been shown to be important for development of Th2-mediated diseases such as asthma through the use of mouse models in vivo. Thymic Stromal LymphoPoietin (TSLP), an IL7-like cytokine, has been shown to potently induce atopic immune responses and is highly expressed at sites of allergic inflammation. While the ability of TSLP to effectively induce an atopic immune cascade has been demonstrated through the use of transgenic mice, direct downstream in vivo mediators have not been identified. In our current study, we show that OX40L is a critical mediator of TSLP-mediated Th2 responses not only in vitro but also in vivo. TSLP strongly induces OX40L expression on dendritic cells and blocking a-OX40L antibodies efficiently inhibit Th2 responses induced by TSLP in vitro, and in the lung and skin in vivo. Inhibition of OX40L function was also very efficacious in decreasing Th2 cytokines and antigen-specific IgE in a mouse model of OVA-induced asthma. The use of blocking a-OX40L antibodies thus presents an effective strategy for the treatment of allergic disease associated with dysregulated Th2 immune responses. The source of research support is Genentech, Inc.
Databáze: OpenAIRE
načítá se...