The analysis of genes involved in the control of Th1/Th2 balance and its role in immune diseases

免疫系统对维持我们的身体以及神经和内分泌系统的稳态起着至关重要的作用。一般来说，我们的身体通过严格的免疫识别和免疫调节机制来保护我们免受各种疾病的侵害。然而，一旦发生免疫调节失衡，就成为各种免疫疾病的病因。最近，人们发现免疫平衡是由两个辅助性T （Th）细胞亚群Th1和Th2调节的。因此，研究Th1/Th2平衡在各种疾病中的作用，对开发新的免疫疾病诊断和治疗方法具有重要意义。在此，我们研究了Th1/Th2平衡的控制机制及其在免疫疾病中的作用。此外，我们还对基因控制Th1/Th2平衡的相关因素进行了研究，以明确遗传免疫性疾病的相关因素。结果，我们展示了新的发现，如下所述；我们利用抗原特异性Th1和Th2细胞建立了新的肿瘤、过敏和肝损伤动物模型。结果表明，Th1细胞和Th2细胞来源于同一个原生Th细胞，在体内疾病发病过程中表现出完全不同的作用。研究证实了特应性皮炎（AD）患者Th1/Th2平衡的异常。从AD患者获得的CD4+T细胞显示IFN-g产生能力降低。此外，还明确了CD4+CD45RO+记忆T细胞抗PPD的定性和定量缺陷。参与控制Th1/Th2平衡的基因被定位在小鼠染色体上。其中一个候选基因位于IL-4受体a基因附近，该基因与特应性皮炎的发病率有关。

Immune system plays a critical role for maintaining the homeostasis of our body as well as nervous and endocrine systems. Generally, our body is protected from various diseases by a strict immunorecognition and immunoregulation mechanisms. However, once, the imbalance of immunoregulation is occurred, it becomes causes of various immune diseases. Recently, it has been clarified that immune balance is regulated by two helper T (Th) cell subsets, Th1 and Th2. Therefore, it is a great important issue to investigate the role of Th1/Th2 balance in various diseases to develop new diagnosis and treatment for immune diseases. Here, we investigated the control mechanisms of Th1/Th2 balance and its role in immune diseases. Moreover, we also pursued factors involved in genetically controlled Th1/Th2 balance to make clear the factors related to genetic immune diseases.As results, we demonstrated new findings as described in the following ;1. We esiablished new animal models for tumor, allergy and liver injury using antigen-specific Th1 and Th2 cells. It was demonstrated that Th1 and Th2 cells derived from the same naive Th cells exhibited totally distinct role during the onset of diseases in vivo.2. The abnormality of Th1/Th2 balance in atopic dermatitis (AD) patients was demonstrated. CD4+T cells obtained from AD patients revealed reduced IFN-g producing ability. Moreover, quantitative and qualitative defect of CD4+CD45RO+ memory T cells reactive against PPD was clarified.3. The genes involved in the control of Th1/Th2 balance was mapped on mouse chromosomes. One of the candidate genes was located nearby IL-4 receptor a gene, which is related to the incidence of atopic dermatis.