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In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation.
J Clin Invest. 2007 Dec; 117(12):3868-78.JCI

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.

Authors+Show Affiliations

Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18060034

Citation

Seshasayee, Dhaya, et al. "In Vivo Blockade of OX40 Ligand Inhibits Thymic Stromal Lymphopoietin Driven Atopic Inflammation." The Journal of Clinical Investigation, vol. 117, no. 12, 2007, pp. 3868-78.
Seshasayee D, Lee WP, Zhou M, et al. In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J Clin Invest. 2007;117(12):3868-78.
Seshasayee, D., Lee, W. P., Zhou, M., Shu, J., Suto, E., Zhang, J., Diehl, L., Austin, C. D., Meng, Y. G., Tan, M., Bullens, S. L., Seeber, S., Fuentes, M. E., Labrijn, A. F., Graus, Y. M., Miller, L. A., Schelegle, E. S., Hyde, D. M., Wu, L. C., ... Martin, F. (2007). In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. The Journal of Clinical Investigation, 117(12), 3868-78.
Seshasayee D, et al. In Vivo Blockade of OX40 Ligand Inhibits Thymic Stromal Lymphopoietin Driven Atopic Inflammation. J Clin Invest. 2007;117(12):3868-78. PubMed PMID: 18060034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. AU - Seshasayee,Dhaya, AU - Lee,Wyne P, AU - Zhou,Meijuan, AU - Shu,Jean, AU - Suto,Eric, AU - Zhang,Juan, AU - Diehl,Laurie, AU - Austin,Cary D, AU - Meng,Y Gloria, AU - Tan,Martha, AU - Bullens,Sherron L, AU - Seeber,Stefan, AU - Fuentes,Maria E, AU - Labrijn,Aran F, AU - Graus,Yvo M F, AU - Miller,Lisa A, AU - Schelegle,Edward S, AU - Hyde,Dallas M, AU - Wu,Lawren C, AU - Hymowitz,Sarah G, AU - Martin,Flavius, PY - 2007/08/09/received PY - 2007/09/26/accepted PY - 2007/12/7/pubmed PY - 2008/2/13/medline PY - 2007/12/7/entrez SP - 3868 EP - 78 JF - The Journal of clinical investigation JO - J Clin Invest VL - 117 IS - 12 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/18060034/In_vivo_blockade_of_OX40_ligand_inhibits_thymic_stromal_lymphopoietin_driven_atopic_inflammation_ L2 - https://doi.org/10.1172/JCI33559 DB - PRIME DP - Unbound Medicine ER -