PTPN4 Functions in Lymphocytes

PTPN4 在淋巴细胞中的功能

• 批准号: 7530435
• 负责人: NICOLAI Stanislas Cyrille VAN OERS
• 金额: $ 23.55万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-02 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7530435
• 关键词: Affect; Allergic; Autoimmune Diseases; Bacteria; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Complex; Development; Equilibrium; Grant; Helper-Inducer T-Lymphocyte; IL4 gene; Immune response; Immune system; Infection; Interleukin-13; Interleukin-4; Interleukin-5; Knockout Mice; Lead; Listeria monocytogenes; Lymphocyte; Mus; NF-kappa B; Population; Production; Protein Tyrosine Phosphatase; Regulation; Role; T Cell Receptor Signaling Pathway; T memory cell; T-Lymphocyte; Th1 Cells; Th2 Cells; Virus; Virus Diseases; base; cell type; cytokine; in vivo; insight; novel therapeutics; pathogen; response; therapeutic target

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.

描述（由申请人提供）：T细胞在控制感染期间产生的免疫应答类型方面具有关键作用。我们提供的初步证据表明，蛋白酪氨酸磷酸酶PTPN 4参与辅助性T细胞的发展。开发了缺乏PTPN 4的小鼠。对这些小鼠的分析显示，来自这些敲除小鼠的T细胞具有增强的Th 2样细胞因子（包括IL 4、IL-5和IL-13）的产生。这表明PTPN 4在调节Th 2细胞发育中的作用是以前未认识到的。我们将使用PTPN 4缺陷型T细胞来确定1）PTPN 4如何调节Th 2发育和2）确定PTPN 4如何影响体内免疫应答。从我们的研究结果将产生新的机制的见解Th 1和Th 2辅助细胞群的发展。这些研究将揭示由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，可以消除被病毒和细菌感染的细胞。然而，T细胞反应可能是破坏性的，如过敏反应和自身免疫性疾病所证明的。我们确定了蛋白酪氨酸磷酸酶PTPN 4在控制免疫系统中T细胞应答类型中的作用。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。