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The Source Identification Of CD24~+ NKT Cell In The Mouse Liver

Posted on:2016-10-08Degree:MasterType:Thesis
Country:ChinaCandidate:C JinFull Text:PDF
GTID:2284330473961588Subject:Cell biology
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The natural killer T cell, also known as the NKT cell, is an unconventional kind of T lymphocytes, expressing surface markers of not only the T cell but also the NK cell, predominantly recognizing lipid molecules presented by the antigen presenting molecule CD 1d. The NKT cell expresses the constant TCR chain (mouse:Vα14-Jα18; human:Va24-Jα18), which is different from conventional T cells. The NKT cell displays significant immunoregulatory functions:firstly, mature NKT cells can secrete abundant Thl cytokines and have the ability to secrete Th2 cytokines. It also displays killing activity and can directly or indirectly interact with multiple cells such as the DC cell, the B cell, etc.; secondly, various subgroups of the NKT cell manifest different immunoregulatory functions. Diversified NKT subgroups have been found in various tissues by far, and can be divided into three subgroups (NKT1, NKT2, NKT 17) based on the transcription factors needed in the development of the NKT cell. NKT1 is mainly situated in the liver and the spleen; NKT2 is mainly situated in the lung; NKT 17 is mainly situated in peripheral lymph nodes. The newfound IL-10 producing NKT10,with a NK1.1" CD4’phenotype, is primarily located in the adipose tissue, the development of which is independent of PLZF. Various subgroups of the NKT cell display different functions in different tissues, and various subgroups of the NKT cellis an important premise of various functions, and therefore seeking new subgroups of the NKT cell is meaningful to further study on the functions of the NKT cell.In the process of further exploring and investigating new subgroups of the NKT cell, a special group of CD24+NKT cells has been found existing only in the liver and mesenteric lymph nodes among peripheral tissues of the mouse. Based on previous studies, we conducted further phenotype identification on the live CD24+NKT celland found high CD44 expression and low PD1 expression in the live CD24+NKT cell, which was different from the thymus CD24+NKT cell; We found that the expression levels of the CD24+ NKT Tetramer and theCD24- NKT Tetramer in the liver were equivalent, and that the expression level of the CD24+ NKT Tetramer was lower than that of the CD24-NKT Tetramer in the thymus; Meanwhile, we identified the location and the sources of the liver CD24+NKT, and it was verified to be mainly located in the blood sinus of the liver by preliminary experiments, and it was also a special NKT cell subgroup that could be formed from the NKT cell from other tissues subjected to the special microenvironment in the liver. Spleen NKT transfer to CD Id KO mice can develop into liver CD24+ NKT, shows that its development in the liver is not dependent on CD1d. We also found that the CD24+NKT in the liver was not affected by intestinal flora. We want to conduct transcriptome sequencing in an effort to investigate the difference between the liver and the thymus in terms of the CD24+ NKT and the CD24’NKT, We made the determination of sample preparation methods, then we are currently preparing for sequencing. Subsequently, we intended to investigate what functions this group of cells displayed in disease models. Based on the ob/ob mouse models in our lab, we found an increased percentage of CD24+NKT in the liver of the ob/ob mice,but the absolute number of CD24+NKT cell remains the same; Meanwhile, we found that the liver CD24+NKT of the ob/ob mice and could combine more HMGB1.The preliminary identification of the phenotype and the source of the liver CD24+NKT indicates that the special liver NKT cell may play an significant role in the liver. The correlation between the liver CD24+NKT cell and hepatic diseases is our next research hotspot.
Keywords/Search Tags:Mouse Liver, CD24~+ NKT cell, Phenotype, Source, Disease model
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