University Utrecht, Faculty Veterinary Medicine, Department Infectious Diseases and Immunology, Yalelaan, Netherlands.
Expert Opin Ther Targets. 2012 Sep;16(9):849-57. doi: 10.1517/14728222.2012.706605. Epub 2012 Jul 16.
Exploitation of antigen-specific regulatory T cells (Tregs) as critical regulators in the control of chronic inflammatory diseases is hampered by the obscure nature of most disease-relevant autoantigens. Heat shock proteins (Hsp) are possible targets for Tregs due to their enhanced expression in inflamed (stressed) tissues and there is evidence that Hsp can induce anti-inflammatory immunoregulatory T-cell responses.
Recent publications showing that exogenous administration of stress proteins has induced immunoregulation in various models of inflammatory disease have also been shown to be effective in first clinical trials in humans. Now, in the light of a growing interest in T-cell regulation, it is of interest to further explore the mechanisms through which Hsp can be utilized to trigger immunoregulatory pathways, capable of suppressing such a wide and diversified spectrum of inflammatory diseases.
Therapeutic approaches via exploitation of antigen-specific Tregs will benefit from tailor-made combination therapies. Combining current therapeutic approaches with Hsp-specific therapies thereby enhancing natural immune regulation might expedite the entry of antigen-specific regulatory T cells into the therapeutic arsenal of the anti-inflammatory therapeutics.
利用抗原特异性调节性 T 细胞(Tregs)作为控制慢性炎症性疾病的关键调节剂,受到大多数与疾病相关的自身抗原性质不明的阻碍。热休克蛋白(Hsp)由于在炎症(应激)组织中表达增强,可能成为 Tregs 的靶点,并且有证据表明 Hsp 可以诱导抗炎免疫调节 T 细胞反应。
最近的出版物表明,外源性给予应激蛋白在各种炎症性疾病模型中诱导了免疫调节,并且在人类的首次临床试验中也显示出了有效性。现在,鉴于人们对 T 细胞调节的兴趣日益增加,人们有兴趣进一步探讨 Hsp 可用于触发免疫调节途径的机制,这些途径能够抑制如此广泛和多样化的炎症性疾病。
通过利用抗原特异性 Tregs 的治疗方法将受益于定制的联合治疗方法。将当前的治疗方法与 HSP 特异性治疗方法相结合,从而增强天然免疫调节作用,可能会加速抗原特异性调节性 T 细胞进入抗炎治疗的治疗武器库。