• Dhaya Seshasayee, Wyne P Lee, Meijuan Zhou, Jean Shu, Eric Suto, Juan Zhang, Laurie Diehl, Cary D Austin, Y Gloria Meng, Martha Tan, Sherron L Bullens, Stefan Seeber, Maria E Fuentes, Aran F Labrijn, Yvo M F Graus, Lisa A Miller, Edward S Schelegle, Dallas M Hyde, Lawren C Wu, Sarah G Hymowitz, and Flavius Martin.
• Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.
• J. Clin. Invest. 2007 Dec 1; 117 (12): 3868-78.

AbstractThymic stromal lymphopoietin (TSLP) potently induces deregulation of Th2 responses, a hallmark feature of allergic inflammatory diseases such as asthma, atopic dermatitis, and allergic rhinitis. However, direct downstream in vivo mediators in the TSLP-induced atopic immune cascade have not been identified. In our current study, we have shown that OX40 ligand (OX40L) is a critical in vivo mediator of TSLP-mediated Th2 responses. Treating mice with OX40L-blocking antibodies substantially inhibited immune responses induced by TSLP in the lung and skin, including Th2 inflammatory cell infiltration, cytokine secretion, and IgE production. OX40L-blocking antibodies also inhibited antigen-driven Th2 inflammation in mouse and nonhuman primate models of asthma. This treatment resulted in both blockade of the OX40-OX40L receptor-ligand interaction and depletion of OX40L-positive cells. The use of a blocking, OX40L-specific mAb thus presents a promising strategy for the treatment of allergic diseases associated with pathologic Th2 immune responses.

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