Regulatory roles of heme oxygenase-1 in autoinflammation and autoimmunity as a model of Behcet's disease

在本研究中，我们试图验证一种假设，即IL-10/HO-1损害保护功能会触发自身免疫和自体炎症反应，从而导致白塞病(BD)。进一步的分析表明CCR1、STAT4、KLRC4、ERAP1、TLR4、NOD2和MEFV是易感基因，所有这些基因都与获得性免疫系统和先天免疫系统有关。其中，TLR4的遗传贡献与我们先前的发现一致，即TLR4的过度表达与BD患者HO-1的表达缺陷有关，这表明该假说在一定程度上是正确的。此外，最近的研究表明，HO-1在非经典的M2巨噬细胞上优先表达，这表明M1/M2平衡的偏离是BD发生的原因。这一问题将在下一笔赠款(26461469号)中进行研究。

In this study, we try to verify the hypothesis that impaired protective function by IL-10/HO-1 trigger autoimmune and autoinflammatory responses, leading to Behcet disease (BD). Further analyses after GWAS have identified CCR1, STAT4, KLRC4, ERAP1, TLR4, NOD2, and MEFV as susceptible genes, all of which are involved in the acquired and innate immunity systems. Of them, genetic contribution of TLR4 is concordant with our previous finding that overexpression of TLR4 is associated with defective expression of HO-1 in BD patients, suggesting validity of the hypothesis in part. Moreover, recent studies have shown that HO-1 is preferentially expressed on non-classical M2 macrophages, suggesting M1 deviation of M1/M2 balance is responsible for development of BD. The issue will be studied in the next grant (No. 26461469).