In Vivo Blockade of OX40 Ligand Inhibits Thymic Stromal Lymphopoietin Driven Atopic Inflammation

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2007 Dec 7

PMID 18060034

Citations 106

Authors

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

Flavius Martin

Affiliations

Soon will be listed here.

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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