Role of IL-12 family cytokines in human autoimmune Uveitis
Role of IL-12 family cytokines in human autoimmune Uveitis
批准号:
10019976
负责人:
Charles E Egwuagu
金额:
$47.64万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
ATAC-seqAdoptive ImmunotherapyAutoimmune DiseasesB-LymphocytesBloodBone MarrowCNS autoimmune diseaseCellsChIP-seqChronicCytokine SignalingDifferentiation and GrowthDiseaseFamilyGenetic EngineeringGoalsGreater sac of peritoneumHumanImmunityInflammatoryInterleukin-10Interleukin-12Lymphocyte FunctionMultiple SclerosisMusNeurodegenerative DisordersPathogenesisPlayRetinaRoleSpleenUveitisautoimmune uveitiscytokineexosomeinterleukin-23membernovelsingle-cell RNA sequencingtherapeutic cytokinestranscriptome
中文摘要
在这项研究中,我们调查的机制,调节B细胞(BCRs)抑制中枢神经系统自身免疫性疾病,如葡萄膜炎或多发性硬化症。这些研究集中于分泌IL-10、IL-27或IL-35的Bcells。我们已经从人血液或骨髓中分离出这些布雷格细胞,在小鼠中,它们从脾脏或腹膜腔中分离。我们现在正在通过单细胞RNA-Seq(scRNA-Seq)、Chip-Seq、ATAC-Seq来表征布雷格细胞转录组。我们还从产生IL-35的白细胞介素(IL-35-BclD)中分离出含有IL-35的外泌体,证明它们抑制实验性自身免疫性葡萄膜炎(EAU),表明来源于BclD的外泌体可用于CNS自身免疫性和神经退行性疾病的过继免疫治疗。
英文摘要
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.
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Role of STAT1 and SOCS in Dendritic cell Differentiation
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依托单位:
海外基金