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The innate immune system modulates the severity of multiple sclerosis

The autoimmune disease multiple sclerosis starts when T cells enter the brain and spinal cord where they mistakenly destroy myelin surrounding nerve fibers. Scientists are working to better understand why T cells enter these areas, which could in turn lead to better prevention or treatment of this disease.

Multiple sclerosis, a debilitating neurological disease, is triggered by self-reactive T cells that successfully infiltrate the brain and spinal cord where they launch an aggressive autoimmune attack against myelin, the fatty substance that surrounds and insulates nerve fibers. Over time, the resulting bouts of inflammation permanently damage the myelin sheath and the nerve fibers it protects, disrupting nerve signals traveling to and from the brain.

But the molecular cues that enable autoimmune T cells, which are usually kept at bay by the blood-brain barrier, to slip into the central nervous system had remained unclear. In their latest study, published in the Nov. 2, 2015, advance online issue ofNature Immunology, researchers at the La Jolla Institute for Allergy and Immunology report that these disease-causing autoimmune T cells are lured into the nervous system by monocytes and macrophages, a subset of immune cells better known as the immune system’s cleanup crew.

“Our results show that macrophages and monocytes actively participate in the initiation and progression of multiple sclerosis, which has long been considered a primarily T cell driven disease,” says the study’s senior author Catherine Hedrick, Ph. D., a professor in the Division of Inflammation Biology. “They exacerbate the severity of the disease by sending out chemical signals that boost inflammation and attract autoimmune T cells to the central nervous system.”

By revealing the molecular mechanisms that control neuroinflammation, these findings add a new layer of complexity to our understanding of multiple sclerosis and support the growing appreciation of the significance of the crosstalk between the peripheral immune system and the brain. They also open up new avenues for potential multiple sclerosis therapies via manipulating the levels of immune regulators that contribute to inflammation in the central nervous system.

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