T cells have a critical role in controlling the type of immune response generated during an infection. We provide preliminary evidence that a protein tyrosine phosphatase termed PTPN4 is involved in T helper cell development. Mice lacking PTPN4 were developed. Analyses of these mice revealed that the T cells from these knock out mice had an enhanced production of Th2-like cytokines including IL4, IL-5, and IL-13. This indicates a previously unrecognized contribution of PTPN4 in the regulation of Th2 cell development. We will use the PTPN4- deficient T cells to determine how 1) PTPN4 regulates Th2 development and to 2) ascertain how PTPN4 influences immune responses in vivo. The findings from our studies will yield new mechanistic insights into the development of Th1 and Th2 helper cell populations. The studies will reveal new therapeutic targets during allergic responses and autoimmune diseases regulated by T helper cell subsets. PROJECT NARRATIVE: T cells are essential for the immune system, eliminating cells infected with viruses and bacteria. Yet, T cell responses can be damaging as evidenced by allergic responses and autoimmune diseases. We identified a role for the protein tyrosine phosphatase, PTPN4, in controlling the type of T cell response in the immune system. Understanding the development of different T cell types will lead to new strategies for controlling allergic responses and autoimmune diseases.
| Young, Jennifer A; Becker, Amy M; Medeiros, Jennifer J et al. (2008) The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable for T cell development and/or T cell effector functions. Mol Immunol 45:3756-66 |
