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- Title
In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation.
- Authors
Seshasayee, Dhaya; Lee, Wyne P; Zhou, Meijuan; Shu, Jean; Suto, Eric; Zhang, Juan; Diehl, Laurie; Austin, Cary D; Meng, Y Gloria; Tan, Martha; Bullens, Sherron L; Seeber, Stefan; Fuentes, Maria E; Labrijn, Aran F; Graus, Yvo M F; Miller, Lisa A; Schelegle, Edward S; Hyde, Dallas M; Wu, Lawren C; Hymowitz, Sarah G; Martin, Flavius
- Abstract
Thymic 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.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 12, p3868
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI33559