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Morrbid gene fights infection havoc
The gene for a lncRNA called Morrbid was identified in 2013 by Henao-Mejia when a postdoctoral fellow in the lab of Richard Flavell, PhD, FRS, at Yale University, the study's coauthor, in collaboration with another coauthor, Adam Williams, The Jackson Laboratory for Genomic Medicine, Bar Harbor, Maine.
The human genome contains about 20,000 protein-coding genes – less than 2 percent of the total genome. But, 70 percent of the human genome actively produces about 10,000 lncRNAs — and the function of the majority of them is unknown.
However, these cell types make up 70 percent of all circulating white blood cells and induce very potent in reactions. Sometimes, reactions so strong they cause damage to surrounding healthy tissue. This reactive system is akin to human first responders appearing at a crisis to lend immediate aid. But, how does the body keep this initial over-zealous-guard-dog response in check? How does the body know when and how to tell the cells to back off?
Morrbid regulates cell lifespan by controlling the expression of Bim, a nearby gene that in turn controls programmed cell death in response to the amount of cytokines and metabolites in the environment surrounding cells. Morrbid essentially overrides signaling that prevents immune cells' premature death.
By deleting Morrbid in mice, the team saw a drastic reduction in immune cells that normally express Morrbid. Therefore, mice had less ability to fight infection — but did gain protection against inflammation.
The expression of the human version of the gene, MORRBID, is impaired in patients with Hypereosinophilic Syndrome (HES). In that sydrome, the lifespan of certain immune cells is not kept in check, resulting in organ damage from continuous inflammation. Yet, in one reported case of a woman with a seven year history of HES, her pregnancy resulted in the delivery of a healthy infant without complications, and no evidence of elevated eosinophils in the infants blood. During pregnancy the patient experienced significant reduction of eosinophils in her blood and resolution of signs and symptoms related to hypereosinophilia.
Search terms: Gene regulation in immune cells Immune cell death
This work was funded by the National Institutes of Health (R21AI110776-01 T32-DK00778017, F30-DK094708, T32-AI05542803, 1DP2OD008514, 1R33EB019767), The Institute for Immunology at Penn, the Howard Hughes Medical Institute, and The Children's Hospital of Philadelphia.
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lncRNAs involved in the control of organ differentiation and development