PTPN2 negatively regulates macrophage immune responses and cellular bioenergetics
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PTPN2 is encoded by the protein tyrosine phosphatase N2 (also known as TC-PTP) and is a negative regulator of cytokine signaling and macrophage differentiation. In the past decade, our work and others', including several pharmaceuticals, have emphasized that inhibition of PTPN2 and PTPN1 (also known as PTP1B) may act as a new first-of-class cancer immunotherapeutic. Although the potential roles of these two enzymes in various immune cells have been broadly reported, the specific activity of PTPN2 in regulating macrophage immune and metabolic responses has yet to be fully elucidated. Hence, we sought to investigate the specific role of PTPN2 in macrophage polarization and function. We used two different mouse models to systematically and specifically inhibit the expression of PTPN2 in macrophages and utilized a chemical inhibitor with a macrophage human cell line to assess their immune and metabolic profiles. We demonstrated that PTPN2 ablation in macrophages alters their immunometabolic..., Bone marrow-derived macrophages (BMDMs) were isolated from PTPN2 wild-type (WT), heterozygous (HET) and knockout (KO) mice. BMDMs were differentiated into M0 macrophages and polarized towards pro-inflammatory M1 and anti-inflammatory M2 macrophages. RNA from purified BMDMs was isolated in TriZOL. Samples were subjected to RNA-sequencing (RNA-Seq) using an Illumina HiSeq 2500. This data contains the raw sequencing reads. , , # PTPN2 negatively regulates macrophage immune responses and cellular bioenergetics Dataset DOI: [10.5061/dryad.7h44j1040](10.5061/dryad.7h44j1040) ## Description of the data and file structure This dataset contains the data derived from bone marrow-derived macrophages (BMDMs) of BALB/c mice, specifically PTPN2 wild-type (WT), heterozygous (HET) and knockout (KO) mice. BMDMs were differentiated *ex vivo* into M0 macrophages and polarized towards pro-inflammatory M1 macrophages with LPS and IFN-ɣ, or towards anti-inflammatory M2 macrophages with IL-4. We were testing the hypothesis that the protein tyrosine phosphatase PTPN2 is important in regulating macrophage phenotype and function. Data cover 3 mice per genotype (WT, HET, KO) per polarization status (M0, M1, M2) for a total of 27 mice. RNA from purified BMDMs was isolated in TriZOL. Samples were subjected to RNA-sequencing (RNA-Seq) using an Illumina HiSeq 2500. This data contains the raw sequencing reads. ### Files and varia..., ,
PTPN2由蛋白酪氨酸磷酸酶N2（protein tyrosine phosphatase N2，也称为TC-PTP）编码，是细胞因子信号转导与巨噬细胞分化的负调控因子。近十年来，本团队及其他研究团队（包括多家制药企业）的研究均证实，抑制PTPN2与PTPN1（也称为PTP1B）有望成为新型首创类癌症免疫疗法。尽管已有大量研究报道了这两种酶在各类免疫细胞中的潜在功能，但PTPN2在调控巨噬细胞免疫与代谢应答中的具体活性仍有待全面阐明。因此，本研究旨在探究PTPN2在巨噬细胞极化与功能发挥中的特异性作用。我们采用两种不同的小鼠模型，系统性且特异性地抑制巨噬细胞中PTPN2的表达，并利用靶向巨噬细胞的化学抑制剂处理人源细胞系，以评估其免疫与代谢特征。我们证实，巨噬细胞中PTPN2的敲除会改变其免疫代谢特征……我们从PTPN2野生型（WT）、杂合型（HET）与敲除型（KO）小鼠中分离骨髓来源巨噬细胞（bone marrow-derived macrophages, BMDMs）。将BMDMs分化为M0型巨噬细胞，并极化为促炎型M1与抗炎型M2巨噬细胞。使用TriZOL试剂提取纯化后BMDMs的总RNA，采用Illumina HiSeq 2500平台进行RNA测序（RNA-sequencing, RNA-Seq）。本数据集包含原始测序读段。 # PTPN2负调控巨噬细胞免疫应答与细胞能量代谢 数据集DOI：[10.5061/dryad.7h44j1040] ## 数据与文件结构说明 本数据集来源于BALB/c小鼠的骨髓来源巨噬细胞（BMDMs），具体涵盖PTPN2野生型（WT）、杂合型（HET）与敲除型（KO）小鼠的样本。我们将BMDMs在体外（ex vivo）分化为M0型巨噬细胞，并分别用脂多糖（LPS）与干扰素γ（IFN-γ）诱导极化为促炎型M1巨噬细胞，用白细胞介素4（IL-4）诱导极化为抗炎型M2巨噬细胞。本研究旨在验证"蛋白酪氨酸磷酸酶PTPN2在调控巨噬细胞表型与功能中发挥关键作用"这一假说。实验设计为：每种基因型（WT、HET、KO）对应每种极化状态（M0、M1、M2）各3只小鼠，总计27只小鼠。 使用TriZOL试剂提取纯化后BMDMs的总RNA，采用Illumina HiSeq 2500平台进行RNA测序（RNA-Seq）。本数据集包含原始测序读段。 ### 文件与变量……
