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Publication : Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation.

First Author  Sibilano R Year  2011
Journal  J Leukoc Biol Volume  90
Issue  4 Pages  831-8
PubMed ID  21653238 Mgi Jnum  J:177546
Mgi Id  MGI:5295363 Doi  10.1189/jlb.1210651
Citation  Sibilano R, et al. (2011) Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcepsilonRI-dependent mast cell degranulation. J Leukoc Biol 90(4):831-8
abstractText  Tregs play a central role in modulating FcepsilonRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-gamma2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.
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