Protein May Control Multiple Sclerosis Severity

The severity of multiple sclerosis (MS) disease activity can be moderated by the innate immune system, according to a study published in Nature Immunology.

Researchers from La Jolla Institute for Allergy and Immunology used mice models of induced MS in order to address the importance of a protein known as Nr4a1 in the brain’s autoimmunity. The researchers said the protein responds to inflammatory and stress signals and they hypothesized that it may by a key factor in the prevention of autoimmunity affecting the central nervous system. The mice models of MS were induced to respond to the protein.

When the mice without the protein had MS, the T cells flooded the central nervous system earlier and with greater volume than compared to the group with MS and the protein. Furthermore, the researchers found that the protein repressed the production of norepinephrine. In the absence of the protein, monocytes and macrophages increased their secretion of norepinephrine — leading to a vicious cycle of macrophage activation followed by subsequent neuroinflammation and an increased amount of T cells flooding the central nervous system, the researchers said.

“Myeloid cells including macrophages have receptors for stress signaling molecules, which allows them to respond to cues from the sympathetic nervous system,” the study’s co-first author Richard Hanna, PhD, explained in a press release. “But is seems they not only listen to the nervous system but that they can also send their own signals.”

The statement added that the norepinephrine production was limited by the Nr4a1 protein, which regulated the amount of tyrosine hydroxylase, the enzyme that controls a bottleneck in the biosynthesis of norepinephrine. In the absence of Nr4a1, the authors said, tyrosine hydroxylase is more present in monocytes and macrophages, which can contribute to disease severity.

“Monocytes and macrophages have a way to amplify inflammation in the central nervous system, which really shows that myeloid cells play an unexpected and important role in diseases of the brain,” postdoctoral researcher Iftach Shaked, PhD, concluded in the statement.