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

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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.