Cedars-Sinai researchers have identified a gene that plays a critical role in the innate human immune system. The gene, NLRP11helps activate the inflammatory response that commands the body’s white blood cells to attack a foreign presence.
The findings, published in Natural immunologybring medical science closer to understanding a biological process that can both help and harm the body.
“Chronic inflammation is an underlying cause of countless human diseases,” said Christian Stehlik, PhD, study co-lead author and director of pathology research at Cedars-Sinai. “If you study the molecular mechanisms involved in how inflammation occurs and how it is regulated, you find something that can be applied very broadly.”
When the immune system detects a bacteria, virus, toxin, or other foreign presence in the body, it sends white blood cells to surround the unwanted substance and release chemicals to attack it. This response leads to inflammation, which causes redness, pain, warmth, and swelling in the affected area as the body heals. Sometimes this defensive response lasts longer than it should, leading to chronic inflammation. Or, the immune system may mistakenly attack healthy cells, leading to autoimmune disease.
“Acute inflammation is necessary and beneficial to eradicate infection and initiate wound healing,” said Andrea Dorfleutner, PhD, study co-lead author and associate professor in the Cedars Departments of Academic Pathology and Biomedical Sciences. -Sinai. “Chronic, long-term, uncontrolled inflammation, however, is detrimental and can damage organs and tissues in the body.”
The key to controlling the inflammatory response and preventing chronic inflammation may lie in the ability to influence the expression of the NLRP11 embarrassed.
The researchers used a gene-editing system called CRISPR/Cas9 to delete genes or introduce genetic mutations into human white blood cells called macrophages. They observed that when they removed NLRP11it prevented an immune system sensor called the NLRP3 inflammasome from being activated and triggering the inflammatory response.
When investigators restored the NLRP11 gene, the NLRP3 inflammasome sent its attack signals, which triggered the typical inflammatory process. The researchers chose to focus on this particular gene because it is not expressed in mice, which led them to hypothesize that it was an integral part of the complex immune system that exists in humans. man.
“Now that we have a better picture of the mechanisms driving inflammation, we can come up with completely new strategies to target it that wasn’t possible before,” Dorfleutner said.
The study’s first authors are Anu Gangopadhyay, Savita Devi, PhD, and Shivendra Tenguria, PhD, all researchers from the Stehlik and Dorfleutner lab.
Funding: The study was funded by the National Institutes of Health (award numbers AI099009, AR064349, AI134030, AI140702, AI165797, and AI120625) and the American Heart Association (award number 834502).
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Material provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.