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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.

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Authors+Show Affiliations

Seshasayee D
Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.
Lee WP
No affiliation info available
Zhou M
No affiliation info available
Shu J
No affiliation info available
Suto E
No affiliation info available
Zhang J
No affiliation info available
Diehl L
No affiliation info available
Austin CD
No affiliation info available
Meng YG
No affiliation info available
Tan M
No affiliation info available
Bullens SL
No affiliation info available
Seeber S
No affiliation info available
Fuentes ME
No affiliation info available
Labrijn AF
No affiliation info available
Graus YM
No affiliation info available
Miller LA
No affiliation info available
Schelegle ES
No affiliation info available
Hyde DM
No affiliation info available
Wu LC
No affiliation info available
Hymowitz SG
No affiliation info available
Martin F
No affiliation info available

MeSH

AnimalsAntibodies, MonoclonalCells, CulturedCricetinaeCytokinesDisease Models, AnimalHumansHypersensitivity, ImmediateImmunoglobulin EInflammationLungMacaca mulattaMembrane GlycoproteinsMiceMice, Inbred BALB CMice, TransgenicOX40 LigandReceptors, OX40SkinTh2 CellsTumor Necrosis Factor InhibitorsTumor Necrosis Factors

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 -