PTPN4 Functions in Lymphocytes

描述(由申请人提供)：T细胞在控制感染期间产生的免疫反应类型方面起着关键作用。我们提供的初步证据表明，一种名为PTPN4的蛋白酪氨酸磷酸酶参与了T辅助细胞的发育。建立PTPN4缺失小鼠模型。对这些小鼠的分析表明，这些基因敲除小鼠的T细胞具有增强的Th2样细胞因子的产生，包括IL4、IL-5和IL-13。这表明PTPN4在Th2细胞发育调节中的作用是以前未知的。我们将使用PTPN4缺乏的T细胞来确定1)PTPN4如何调节Th2的发育，以及2)PTPN4如何影响体内的免疫反应。我们的研究结果将为Th1和Th2辅助细胞群体的发展提供新的机制见解。这些研究将揭示T辅助细胞亚群调节的过敏反应和自身免疫性疾病的新治疗靶点。项目简介：T细胞对免疫系统至关重要，可以清除感染病毒和细菌的细胞。然而，T细胞反应可能是破坏性的，过敏反应和自身免疫性疾病就是明证。我们确定了蛋白酪氨酸磷酸酶PTPN4在免疫系统中控制T细胞反应类型中的作用。了解不同T细胞类型的发展将导致控制过敏反应和自身免疫性疾病的新策略。

DESCRIPTION (provided by applicant): 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.