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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3868-3878 |
| Number of pages | 11 |
| Journal | Journal of Clinical Investigation |
| Volume | 117 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2007 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. / 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; Schelegle, Edward S; Hyde, Dallas M.; Wu, Lawren C.; Hymowitz, Sarah G.; Martin, Flavius.
In: Journal of Clinical Investigation, Vol. 117, No. 12, 12.2007, p. 3868-3878.Research output: Contribution to journal › Article
}
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
AU - Schelegle, Edward S
AU - Hyde, Dallas M.
AU - Wu, Lawren C.
AU - Hymowitz, Sarah G.
AU - Martin, Flavius
PY - 2007/12
Y1 - 2007/12
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.
AB - 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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U2 - 10.1172/JCI33559
DO - 10.1172/JCI33559
M3 - Article
VL - 117
SP - 3868
EP - 3878
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -