SPMAC: The role of pro-resolving lipid mediators and gut-resident macrophages in regulating early-in-life immune imprinting and adulthood [...]

当我们在断奶期间从牛奶转向固体食物时，肠道内细菌的数量和类型都会增加。作为回应，我们的身体会对越来越多的细菌产生防御。有趣的是，这种反应是我们防御系统的第一次训练或“印记”。它教会我们的防御细胞区分有益和有害的细菌，并以一种平衡的方式对外来微生物作出反应，而不会对身体造成太大的损害，也不会加剧炎症反应，而炎症反应是我们身体的主要防御手段。如果这一最初的训练步骤被打乱，机体就会形成一种不适当的印记，并在整个生命中保留下来，从而增加成年期对炎症性疾病的易感性，包括结肠炎。这些疾病的发生是因为我们的身体夸大了炎症反应，但我们仍然不知道这是如何发生的。因此，这项提议的目的是回答一些仍然没有答案的相关问题：我们身体产生的哪些细胞和分子对这种印记很重要？这些分子在生命后期的应用能否逆转早期不适当的印记，从而控制成年期对结肠炎的易感性？这些答案可以帮助我们了解像结肠炎这样的炎症性疾病是如何发展的，并揭示更有效的控制或治疗方法。

As we transition from milk to solid foods during weaning, the number and types of bacteria in our intestine increases. In response, our body develops defenses against the increasing number of bacteria. Interestingly, this response works as the first training or "imprinting" for our defenses systems. It teaches our defense cells to distinguish between beneficial and harmful bacteria, and to react in a balanced way against foreign microorganisms without causing too much damage to the body or exaggerate in the inflammatory response that is our body's main means of defense. If this initial training step is disrupted, the organism develops an improper imprinting that is retained throughout life, increasing the susceptibility to inflammatory diseases in the adulthood, including colitis. These diseases occur because our body exaggerates in the inflammatory response, but we still do not know how this occurs. Thus, the aim of this proposal is to answer some pertinent questions for which there is still no answer: What cells and molecules produced by our body are important for this imprinting? Could the application of such molecules later in life reverse cases of an improper early-in-life imprinting and, thus, control the susceptibility to colitis in the adulthood? These answers can help us understand how inflammatory diseases like colitis develop and reveal more effective approaches to control or treat them.