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REGULATORY T CELLS GENETICALLY MODIFIED FOR THE LYMPHOTOXIN ALPHA GENE AND USES THEREOF

机译:基因修饰的淋巴毒素α基因的调节性T细胞及其用途

摘要

The present invention relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LTα, which negatively regulates their immunosuppressive signature. They demonstrated that the adoptive transfer of LTα-/- Tregs in mice protects from dextran sodium sulfate (DSS)-induced colitis and attenuates inflammatory bowel disease (IBD), multi-organ autoimmunity and the development of CAC. The inventors also showed that by mixed bone marrow chimeras that LTα expression specifically in hematopoietic cells negatively controls the immunosuppressive signature of Tregs. In particular, the present invention relates to regulatory T cell characterized in that it does not express or expresses reduced levels of lymphotoxin alpha.
机译:本发明涉及调节性T细胞及其用途。通过其免疫抑制和抗炎活性,调节性T细胞在外周耐受中起着核心作用,因此可关键地预防自身免疫和炎性疾病的发展。发明人表明Foxp3 + CD4 + Tregs表达高水平的LTα,其负调节其免疫抑制特征。他们证明了小鼠中LTα-/-Tregs的过继转移可防止葡聚糖硫酸钠(DSS)诱导的结肠炎,并减轻炎症性肠病(IBD),多器官自身免疫和CAC的发展。发明人还表明,通过混合的骨髓嵌合体,在造血细胞中特异性地LTα表达负调控Treg的免疫抑制特征。特别地,本发明涉及调节性T细胞,其特征在于其不表达或表达降低水平的淋巴毒素α。

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