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Regulation of inflammation and homeostatsis of oral mucosal tissue by dendritic cells.

机译：树突状细胞对口腔粘膜组织的炎症和稳态的调节。

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摘要

Dendritic cells (DCs) are very effective at recognizing, capturing and processing antigens, and after activation, are highly effective antigen presenting cells. DC plays an important role in coordinating innate and adaptive immune response against pathogens. DCs are also likely to balance tolerance and active immunity to commensal microorganisms as part of chronic inflammatory responses.;Two independent studies were conducted to elucidate the role dendritic cells contribute to the tissue integrity. In the first part of my thesis, I found that osteoprotegerin (OPG) knockout (KO) DCs survive better than wild type (WT) DCs and produce more TNF-alpha, IL-12p40, and IL-23 than WT DCs in response to E. coli LPS. This is due to sustained interactions between DCs, which increases both the longevity of OPG KO DCs and the level of proinflammatory cytokines produced by OPG KO DCs. Disruption of DC-DC interactions by OPG treatment reduced both the survival of and cytokine production by WT DCs. In addition, after inoculation with LPS, OPG KO mice produce more TNF-alpha and IL-12p40 than WT mice. My results suggest that OPG regulates survival and cytokine production of DCs, thereby affecting the nature of inflammatory responses.;In the second part of my thesis, I found that all oral bacteria tested could efficiently program DCs. Oral bacteria stimulated human monocyte-derived immature DCs to mature and to secrete cytokines/chemokines. Surprisingly, the most important factor for programming DCs was not whether the oral bacteria were commensals or pathogenic, but whether they were gram-positive or gram negative. Fewer gram-negative bacteria were required than gram-positive bacteria to induce DC maturation. Gram-negative oral bacteria also had a lower threshold for cytokine induction than gram-positive oral bacteria. I also found that the threshold of bacteria required for chemokine induction was 100-1000 fold lower than for inducing cytokines In addition, at very low doses of oral commensal bacteria, monocytes were triggered to migrate toward DC-derived MCP-1. Thus, DC-derived MCP-1 induced in response to oral commensal bacteria may play, at least in part, a role in the maintenance of oral tissue integrity by attracting monocytes.
机译：树突状细胞（DC）在识别，捕获和加工抗原方面非常有效，并且在激活后是高效的抗原呈递细胞。 DC在协调针对病原体的先天性和适应性免疫应答中起重要作用。 DCs也可能平衡对共生微生物的耐受性和主动免疫，这是慢性炎症反应的一部分。进行了两项独立研究，以阐明树突状细胞对组织完整性的贡献。在论文的第一部分中，我发现骨保护素（OPG）敲除（KO）DC比野生型（WT）DC生存更好，并且比WT DC产生更多的TNF-alpha，IL-12p40和IL-23。大肠杆菌LPS。这是由于DC之间持续的相互作用，这既增加了OPG KO DC的寿命，又增加了OPG KO DC产生的促炎细胞因子的水平。通过OPG处理破坏DC-DC相互作用会降低WT DC的存活率和细胞因子的产生。此外，接种LPS后，OPG KO小鼠比WT小鼠产生更多的TNF-α和IL-12p40。我的结果表明，OPG调节DC的存活和细胞因子的产生，从而影响炎症反应的性质。在论文的第二部分，我发现测试的所有口腔细菌都能有效地编程DC。口腔细菌刺激人单核细胞衍生的未成熟DC成熟并分泌细胞因子/趋化因子。令人惊讶地，对DC进行编程的最重要因素不是口腔细菌是共生的还是致病的，而是它们是革兰氏阳性还是革兰氏阴性。诱导DC成熟所需的革兰氏阴性菌要少于革兰氏阳性菌。革兰氏阴性口腔细菌的细胞因子诱导阈值也低于革兰氏阳性口腔细菌。我还发现，趋化因子诱导所需的细菌阈值比诱导细胞因子低100-1000倍。此外，在非常低剂量的口服共生细菌的情况下，单核细胞被触发向DC衍生的MCP-1迁移。因此，响应口腔共生细菌而诱导的DC衍生的MCP-1可通过吸引单核细胞至少部分地在维持口腔组织完整性中起作用。

著录项

  • 作者

    Chino, Takahiro.;

  • 作者单位

    University of Washington.;

  • 授予单位 University of Washington.;
  • 学科 Biology Microbiology.;Health Sciences Dentistry.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 90 p.
  • 总页数 90
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;口腔科学;预防医学、卫生学;
  • 关键词

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