Discovering new genes involved in protective T-cell responses through the generation of mice with targeted mutations
Discovering new genes involved in protective T-cell responses through the generation of mice with targeted mutations
批准号:
10042745
负责人:
Luis J Sigal
金额:
$23.4万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-06-01 至 2022-05-31
关键词:
AdoptedAnimalsAntibodiesAntigensAntiviral AgentsAntiviral ResponseAreaAutoimmune DiseasesBiologyBone MarrowCD3 AntigensCD44 geneCD8-Positive T-LymphocytesCD8B1 geneCellsCessation of lifeChimera organismCommunicable DiseasesCytotoxic T-LymphocytesDevelopmentDiseaseEnzymesExonsFlow CytometryFutureGene DeletionGenerationsGenesGenetic TranscriptionGonadal structureGrantGranzymeHematopoieticHumanImmuneImmune System DiseasesImmune responseImmune systemImmunologic Deficiency SyndromesImmunologyInbred BALB C MiceInfectionInfectious EctromeliaKnowledgeLeukocytesLiverLoxP-flanked alleleMaintenanceMalignant NeoplasmsMammalian OviductsMemoryMethodsModelingMouse Pox VirusMouse StrainsMusMutationPTPRC genePeripheralPlayPopulationProteinsRNAReporterResistanceRoleSiteSpleenSplenocyteStainsT cell responseT-Cell ActivationT-Cell DevelopmentT-LymphocyteTamoxifenThymus GlandVaccinesViral Drug ResistanceViral load measurementVirus DiseasesWorkcancer therapycombatcostcytotoxicdifferential expressionexperiencegene discoverygene functiongenome editinghepatic necrosishigh riskimmune resistanceimprovedin vivoinfectious disease treatmentinnovationinsightmouse modelnovelnucleic acid deliverypathogenpreventresistant strainresponsetranscriptome sequencingtranslational impactvaccine effectiveness
中文摘要
摘要
T细胞在抗击传染病和癌症方面发挥着重要作用,对
疫苗的有效性,并可能对各种类型的免疫疾病产生负面影响。
虽然与T细胞反应有关的许多基因已经被识别出来,但很可能有许多
仍然不为人所知。这些基因的发现及其在体内免疫中的特殊作用
反应可以为我们对免疫系统的理解和
改进疫苗和/或治疗传染病、癌症和各种疾病
免疫紊乱。在这里,我们建议用T细胞缺失的基因来产生小鼠
在保护抗病毒T细胞过程中,特定T细胞群的转录受到干扰
回应。我们的假设是,这些基因中的一些将在免疫中发挥重要作用
对病原体的反应以及可能在癌症和各种免疫功能障碍中的作用。鼠标
通过这笔赠款开发的模型将提供关于蒸馏器角色的新的有价值的信息
鲜为人知的基因在调节抗病毒免疫反应和抵抗病毒中的作用
感染,可能是未来新发现的基础,不仅包括免疫学
但哺乳动物生物学的其他领域。
英文摘要
Abstract
T-cells play major functions to combat infectious diseases and cancer, are critical for the
effectiveness of vaccines, and may have negative effects in various types of immune disorders.
While many of the genes involved in T-cell responses have been identified, it is likely that many
remain unknown. The discovery of these genes and their specific roles during in vivo immune
responses could provide major advances in our understanding of the immune system and for
the improvement of vaccines and/or treatment of infectious diseases, cancer, and various
immune disorders. Here we propose to generate mice with T-cell deletions of genes whose
transcription is perturbed in specific T-cell populations during protective anti-viral T-cell
responses. Our hypothesis is that some of these genes will play essential roles in immune
responses to pathogens and possible in cancer and various immune dysfunctions. The mouse
models developed through this grant will provide new valuable information about the role of still
little-known genes in the modulation of the anti-viral immune response and resistance to viral
infection and may be the basis of future novel discoveries encompassing not only immunology
but other areas of mammalian biology.
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