Methods of modulating TGFβ signaling
The present invention provides methods of identifying the presence of or quantifying the amount of one or more of T helper (Th) cells and iTreg cells present in a sample by identifying the presence of an ADAM or the amount of an ADAM, such as ADAM12, present in a sample. The present invention also provides methods for increasing or decreasing signaling of a TGF such as TGFβ by increasing or decreasing the biological activity or expression of an ADAM. Further, the present invention provides methods for inhibiting or stimulating, downregulating or upregulating, an immune response, and for treating diseases associated with an immune response such as cancer, viral, bacterial and fungal infections, autoimmune diseases and graft versus host diseases. Still further, the invention provides screening methods effective for identifying therapeutic agents, pharmaceutical compositions containing therapeutic agents, and vaccines.
1. A method for decreasing signaling of a TGF in a T cell comprising decreasing the biological activity or expression of an ADAM by administering an agent that functions to inhibit the expression or biological activity of an ADAM wherein the agent is an interfering RNA or an antibody.
2. The method of claim 1 wherein the TGF is TGFβ.
3. The method of claim 1 wherein the ADAM is ADAM12.
4. A method for decreasing signaling of a TGF in a T cell according to claim 1 wherein the T cell is a helper T cell.
5. A method for decreasing signaling of a TGF in a T cell according to claim 1 wherein the T cell is a Th17 cell.
6. A method for decreasing signaling of a TGF in a T cell according to claim 1 wherein the T cell is an iTreg cell.