Faculdade de Biociências e Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Front Immunol. 2012 May 4;3:95. doi: 10.3389/fimmu.2012.00095. eCollection 2012.
Immune responses to heat shock proteins (Hsp) develop in virtually all inflammatory diseases; however, the significance of such responses is only now becoming clear. In experimental disease models, Hsp administration can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory diseases, Hsp peptides have been shown to promote the production of anti-inflammatory cytokines, indicating immunoregulatory potential of Hsp. Therefore, the presence of immune responses to Hsp in inflammatory diseases can be seen as an attempt of the immune system to correct the inflammatory condition. Hsp70 can modulate inflammatory responses in models of arthritis, colitis and graft rejection, and the mechanisms underlying this effect are now being elucidated. Incubation with microbial Hsp70 was seen to induce tolerogenic dendritic cells (DCs) and to promote a suppressive phenotype in myeloid-derived suppressor cells and monocytes. These DC could induce regulatory T cells (Tregs), independently of the antigens they presented. Some Hsp70 family members are associated with autophagy, leading to a preferential uploading of Hsp70 peptides in MHC class II molecules of stressed cells. Henceforth, conserved Hsp70 peptides may be presented in these situations and constitute targets of Tregs, contributing to downregulation of inflammation. Finally, an interfering effect in multiple intracellular inflammatory signaling pathways is also known for Hsp70. Altogether it seems attractive to use Hsp70, or its derivative peptides, for modulation of inflammation. This is a physiological immunotherapy approach, without the immediate necessity of defining disease-specific auto-antigens. In this article, we present the evidence on anti-inflammatory effects of Hsp70 and discuss the need for experiments that will be crucial for the further exploration of the immunosuppressive potential of this protein.
几乎所有的炎症性疾病都会产生针对热休克蛋白 (Hsp) 的免疫反应；然而，这些反应的意义直到现在才变得清晰起来。在实验性疾病模型中，给予 Hsp 可以预防或阻止炎症损伤，并且在慢性炎症性疾病患者的初步临床试验中，已经表明 Hsp 肽能够促进抗炎细胞因子的产生，这表明 Hsp 具有免疫调节潜力。因此，在炎症性疾病中存在针对 Hsp 的免疫反应可以被视为免疫系统试图纠正炎症状态的一种尝试。Hsp70 可以调节关节炎、结肠炎和移植物排斥反应的炎症反应，其作用机制目前正在阐明。与微生物 Hsp70 孵育被认为可以诱导耐受性树突状细胞 (DC)，并促进髓样来源的抑制细胞和单核细胞中的抑制表型。这些 DC 可以独立于它们呈递的抗原诱导调节性 T 细胞 (Treg)。一些 Hsp70 家族成员与自噬有关，导致应激细胞 MHC Ⅱ类分子中优先加载 Hsp70 肽。因此，在这些情况下可能会呈现保守的 Hsp70 肽，并成为 Treg 的靶标，有助于下调炎症。最后，Hsp70 还已知对多种细胞内炎症信号通路具有干扰作用。总的来说，使用 Hsp70 或其衍生肽来调节炎症似乎很有吸引力。这是一种生理性免疫治疗方法，不需要立即定义疾病特异性自身抗原。在本文中，我们介绍了 Hsp70 的抗炎作用证据，并讨论了进行实验的必要性，这些实验对于进一步探索该蛋白的免疫抑制潜力至关重要。
