Role of IL-12 family cytokines in human autoimmune Uveitis

IL-12家族细胞因子在人类自身免疫性葡萄膜炎中的作用

• 批准号: 10019976
• 负责人: Charles E Egwuagu
• 金额: $ 47.64万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10019976
• 关键词: ATAC-seq; Adoptive Immunotherapy; Autoimmune Diseases; B-Lymphocytes; Blood; Bone Marrow; CNS autoimmune disease; Cells; ChIP-seq; Chronic; Cytokine Signaling; Differentiation and Growth; Disease; Family; Genetic Engineering; Goals; Greater sac of peritoneum; Human; Immunity; Inflammatory; Interleukin-10; Interleukin-12; Lymphocyte Function; Multiple Sclerosis; Mus; Neurodegenerative Disorders; Pathogenesis; Play; Retina; Role; Spleen; Uveitis; autoimmune uveitis; cytokine; exosome; interleukin-23; member; novel; single-cell RNA sequencing; therapeutic cytokines; transcriptome

In this study, we investigated mechanisms by which regulatory B cells (Bregs) suppress CNS autoimmune diseases such as Uveitis or Multiple Sclerosis. These studies focused on Bregs that secrete IL-10, IL-27 or IL-35. We have isolated these Breg cells from human blood or bone marrow and in mice they were isolated from the spleen or peritoneal cavity. We are now characterizing the Breg cells transcriptomes by single-cell RNA-Seq (scRNA-Seq), Chip-Seq, ATAC-Seq. We have also isolated IL-35 containing exosomes from IL-35-producing Bregs (i35-Bregs), demonstrated that they suppress experimental autoimmune uveitis (EAU), suggesting that exosomes derived from Bregs can be exploited for adoptive immunotherapy in CNS autoimmune and neurodegenerative diseases.

在这项研究中，我们研究了调节性B细胞(Bregs)抑制CNS自身免疫性疾病(如葡萄膜炎或多发性硬化症)的机制。这些研究集中在分泌IL-10、IL-27或IL-35的Bregs。我们已经从人的血液或骨髓中分离出了这些Breg细胞，在小鼠身上，它们也是从脾或腹膜中分离出来的。我们现在正在用单细胞RNA-Seq(scRNA-Seq)、Chip-Seq、ATAC-Seq来鉴定Breg细胞的转录本。我们还从产生IL-35的Bregs(i35-Bregs)中分离出含有IL-35的外切体(i35-Bregs)，证明它们可以抑制实验性自身免疫性葡萄膜炎(EAU)，这表明Bregs来源的Exosome可以用于中枢神经系统自身免疫性和神经退行性疾病的过继免疫治疗。