Modulation of Th2 lineage commitment by T-bet
OwnerLaurie Glimcher, Susanne Szabo +1inventors
InventorsLaurie Glimcher, Susanne Szabo, Eun Hwang
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Abstract
The instant invention is based, at least in part, on the identification of a mechanism by which T-bet directly modulates Th2 cytokine production. The present invention pertains to methods of identifying agents that modulate the Tec kinase-mediated interaction of T-bet with GATA-3, as well as methods of use therefore.
Claims29
A method for identifying a compound which directly increases Th2 lineage commitment during T cell differentiation, comprising contacting in the presence of the compound, T-bet and a Tec kinase molecule under conditions which allow interaction of the kinase molecule with T-bet;
- and detecting the interaction of T-bet and the kinase molecule, wherein the ability of the compound to directly increase Th2 lineage commitment during T cell differentiation is indicated by a decrease in the interaction as compared to the amount of interaction in the absence of the compound.
A method of identifying compounds useful in directly increasing Th2 lineage commitment during T cell differentiation comprising,
- a) providing an indicator composition comprising ITK, T-bet and GATA3;
- b) contacting the indicator composition with each member of a library of test compounds;
- c) selecting from the library of test compounds a compound of interest that decreases the ITK-mediated interaction of T-bet and GATA3 to thereby identify a compound that directly increases Th2 lineage commitment.
A method for identifying a compound which modulates the interaction of T-bet and GATA3 in a T cell, comprising contacting in the presence of the compound and ITK, T-bet and GATA3 under conditions which allow ITK-mediated binding of T-bet to GATA3 to form a complex;
- and detecting the formation of a complex of T-bet and GATA3 in which the ability of the compound to inhibit interaction between T-bet and GATA3 in the presence of ITK and the compound is indicated by a decrease in complex formation as compared to the amount of complex formed in the absence of ITK and the compound.
A method of identifying compounds useful in directly increasing the production of at least one Th2 cytokine by a T cell, comprising,
- a) providing an indicator composition comprising ITK, T-bet and GATA3;
- b) contacting the indicator composition with each member of a library of test compounds;
- c) selecting from the library of test compounds a compound of interest that decreases the ITK-mediated interaction of T-bet and GATA3 to thereby identify a compound that directly increases the production of at least one cytokine.
A method of treating or preventing a disorder that would benefit from treatment with an agent that directly increases Th2 cytokine production by T cells, comprising administering to a subject with said disorder an agent that decreases the ITK-mediated binding of T-bet and GATA3 in T cells, such that the disorder is treated or prevented.
A method of directly increasing Th2 cytokine production by a T cell, comprising contacting the cell with an agent that decreases the ITK-mediated binding of T-bet and GATA3 in the T cell, such that Th2 cytokine production by the T cell is directly increased.
A method of directly increasing Th2 lineage commitment during T cell differentiation, comprising contacting the cell with an agent that decreases the ITK-mediated binding of T-bet and GATA3 in the T cell, such that Th2 lineage commitment during T cell differentiation is directly increased.
Dependencies are inferred from the claim text.