In a new study in Science Translational Medicine, Stanford rheumatologist and immunologist Connie Weyand, MD, and her colleagues have figured out what sparks the aberrant activation of the immune cells driving the angry inflammation and tissue damage that mark rheumatoid arthritis, an autoimmune disease.
Autoimmune diseases arise when cells of the immune system — whose ire is supposed to be directed at cancer cells and invading pathogens — go haywire and start attacking our own tissues. In rheumatoid arthritis, tendons, cartilage and bone get torn up due to the inappropriate activation of a class of immune cells called T cells, that — although they really shouldn’t — take aim at proteins in these tissues, go on a tear and direct other types of immune cells to do likewise.
The study showed that these T cells have a defect in their internal processing of glucose — the energy currency of all cells — because they’re making too much of a particular enzyme involved in glucose metabolism, shunting that sugar down an alternative metabolic pathway.
That alternative metabolic route, in turn, generates excessive amounts of substances that snuff out free radicals: “musical-chairs molecules” that are missing an electron and will stop at nothing — up to and including ripping other molecules apart — to get hold of one. This sets off a chain of electron-pulling, molecule-splitting mayhem and, if not controlled, can damage the proteins, DNA, and fatty substances that keep cells intact and functioning properly.
Until recently, free radicals were regarded as pure bad news. Antioxidants, which chill out free radicals by furnishing them with electrons, are a popular item in health-food stores and catalogs. One recent estimate has it that the global antioxidants market will reach $4.14 billion by 2022.
But it turns out that free radicals can and do perform valuable signaling services within our cells: among them, the regulation of the cell-cycle machinery – the complex, multi-component biological timer that tells cells whether and how soon to divide into two. (That’s how our cells proliferate and our tissues expand.)
The free-radical-depleting defect, and resulting improper free-radical signaling behavior, not only trips off out-of-control proliferation of joint-tissue-targeting T cells that would ordinarily not be proliferating, but also shifts those cells’ character from being relatively docile toward being inflammatory: i.e., on the warpath.
The good news: A couple of pharmacological interventions proved able to restore intracellular free-radical supplies, correct the rampage-prone T cells’ abnormal proliferation, and, best of all, suppress joint destruction in an experimental model of rheumatoid arthritis.
It’s a long way from that point to the conclusion of a successful round of clinical trials. But for the one in every 80 or so people in the world suffering from rheumatoid arthritis, every step in the right direction is a welcome move.
Previously: Glucose-guzzling immune cells may cook up coronary artery disease, Stanford study finds, Important immune defect identified in immune cells of rheumatoid arthritis patients and Rheumatoid arthritis patients fare better than 20 years ago, study finds
