Table_1_Myosin Light Chain 9/12 Regulates the Pathogenesis of Inflammatory Bowel Disease.xlsx

The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create “Myl9 nets” that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.

全球范围内，炎症性肠病（IBD）患者数量，如溃疡性结肠炎（UC）和克罗恩病（CD）患者数量，随着时间的推移呈现增长趋势；然而，IBD的发病机制复杂多因素，尚未得到全面的理解。肌球蛋白轻链9和12a以及12b（Myl9/12）被认为是CD69分子的配体。它们在炎症部位形成“Myl9网”，该网状结构常被检测到，并在调节表达CD69的效应细胞在炎症组织中的募集和保留方面发挥着至关重要的作用。我们的研究证明了Myl9/12在IBD患者和DSS诱导的结肠炎小鼠的炎症肠道中的强烈表达。对DSS诱导的结肠炎小鼠给予抗Myl9/12抗体治疗，可改善炎症并延长其生存期。在活动性UC和CD患者的血浆中，Myl9水平显著高于疾病缓解期的患者，可能描绘了IBD患者的疾病严重程度，尤其是UC患者。因此，我们的研究结果指示Myl9/12参与了IBD的发病机制，并且很可能成为IBD患者的新治疗靶点。