Department of Pediatric Immunology, Center for Molecular and Cellular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Netherlands.
Front Immunol. 2012 May 31;3:139. doi: 10.3389/fimmu.2012.00139. eCollection 2012.
Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs) are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, "natural" mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases. Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg) function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response. Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene hypothesis.
在过去的几年中，人们对先天免疫和适应性免疫之间复杂相互作用的认识有了极大的提高，这使得人们对热休克蛋白（stress proteins）重新产生了兴趣。这些蛋白质在细胞应激时表达，它们可以吸引和触发免疫反应，因此可以作为这种相互作用的重要介质。在这方面，特别有趣的是那些可能作为先天免疫和适应性免疫调节剂的蛋白质。热休克蛋白（heat shock proteins，HSPs）就是具有这些特性的应激蛋白。对 HSPs 的研究已经进行了二十多年，研究表明它们是内在的、“天然的”调节炎症的机制的一部分。这引发了对 HSPs 在各种人类炎症性疾病中的作用的全面探索。大多数研究都集中在经典的自身免疫性疾病上。这导致了 HSPs 的临床研究的发展，这些研究在 II/III 期临床试验中显示出了希望。值得注意的是，目前人们对 HSPs 在特应性疾病中的作用知之甚少。在过敏性疾病中，有许多研究探讨了过敏原特异性调节性 T 细胞（Treg）功能在过敏性疾病患者中是否存在缺陷的可能性。这就提出了一个问题，即是否可以找到方法来改善 Treg 库。其他炎症性疾病的研究表明，HSPs 可能对 T 细胞库有这种有益的影响。基于特应性疾病的免疫机制，在这篇综述中，我们将认为，正如在其他人类炎症性疾病中一样，对 HSPs 的免疫理解也可能与特应性疾病有关。具体来说，我们将讨论为什么某些 HSPs（如 HSP60）将对环境抗原的免疫反应与炎症反应的调节联系起来。因此，它们提供了一个分子联系，最终甚至可能有助于更好地理解卫生假说的免疫病理基础。
