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Pathogenic potential of CD4 T cells in autoimmune diseases.

机译：CD4 T细胞在自身免疫性疾病中的致病潜力。

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摘要

The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 T helper into subsets, but also influence the identity, plasticity and effector function of a T cell. Th17 cells, named for producing interleukin 17 (IL-17) as their signature cytokine, secrete a cohort of other cytokines including IL-22, IL-21, IL-10, IL-9, IFNgamma, and GM-CSF. In recent years, Th17 cells have emerged as a key player in host defense against both extracellular pathogens and fungal infections. Th17 cells have also been implicated as one of the main drivers in the pathogenesis of autoimmune diseases such as multiple sclerosis, which are likely mediated in part by the cytokines that Th17 cells produce.;Here in this thesis, we explore the pathogenic regulation of CD4 T cells in the context of the autoimmune diseases, multiple sclerosis and inflammatory bowel disease. We attempt to understand the mechanisms by which Th17 cells promote pathogenic inflammation by utilizing high throughput whole genome mRNA sequencing as well as next generation single cell RNA sequencing to uncover novel regulators that drive effector function. Advances in high throughput genomic sequencing allowed us to uncover an unexpected heterogeneity and diversity in Th17 cell populations. The four studies outlined in this thesis reconcile many confounding questions in the areas of autoimmune pathogenicity and reveal key regulators that define the various functional states of Th17 cells.
机译：控制T辅助（Th）细胞分化和功能的分子机制揭示了一个复杂的转录和蛋白质调节剂网络。细胞因子不仅会引发CD4 T辅助细胞分化为亚型，而且还会影响T细胞的特性，可塑性和效应子功能。 Th17细胞以产生白介素17（IL-17）作为其标志性细胞因子而命名，它分泌其他细胞因子的队列，包括IL-22，IL-21，IL-10，IL-9，IFNgamma和GM-CSF。近年来，Th17细胞已成为宿主防御细胞外病原体和真菌感染的关键因素。 Th17细胞也被认为是自身免疫性疾病（如多发性硬化）发病机理的主要驱动因素之一，其可能部分由Th17细胞产生的细胞因子介导。在本文中，我们探讨了CD4的致病性调控。 T细胞是自身免疫性疾病，多发性硬化症和炎症性肠病。我们试图通过利用高通量全基因组mRNA测序以及下一代单细胞RNA测序来揭示Th17细胞促进致病性炎症的机制，以揭示驱动效应子功能的新型调节子。高通量基因组测序的进展使我们能够发现Th17细胞群体中意想不到的异质性和多样性。本文概述的四项研究调和了自身免疫致病性领域中的许多混淆性问题，并揭示了定义Th17细胞各种功能状态的关键调控因子。

著录项

  • 作者

    Lee, Youjin.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Neurosciences.;Immunology.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 240 p.
  • 总页数 240
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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