Aug. 15, 2013 — Multiple sclerosis (MS) is a disease that affects the central nervous system (the brain and spinal cord) with devastating consequences. What causes MS is still unknown, but it is clear that the disease is perpetuated by repeated attacks of the nervous system by cells from a person’s own immune system. Texas A&M University researchers in the College of Veterinary Medicine & Biomedical Sciences and the Texas A&M Institute for Neuroscience have uncovered a pathway that the brain cells use to blunt these attacking immune cells.
Galectin-9 is upregulated in astrocytes by TNF and promotes encephalitogenic T-cell apoptosis
Background: Galectins are increased in astrocytes of patients with multiple sclerosis.
Results: TNF upregulates galectin-9 in primary astrocytes via the TNFR1/JNK/c-Jun pathway and can induce apoptosis of encephalitogenic T cells.
Conclusion: Astrocytes upregulate galectin-9 in response to the proinflammatory cytokine TNF.
Significance: Astrocyte derived galectin-9 may function to restrict encephalitogenic T-cell–mediated inflammation in the CNS.
Andrew Steelman, Roger Smith, Jane Welsh and Jianrong Li have investigated how the brain cells called astrocytes produce a protein named galectin-9 and suppress the autoreactive immune cells that are capable of invading and damaging the central nervous system. Their work is published in The Journal of Biological Chemistry.
“We and others have found that galectin-9 is increased in the MS brain, but what it does is not known,” explains Li, the senior author of the study.
“Because this protein is not normally found in the brain, we were particularly interested in how it becomes induced,” adds Steelman, the lead author of the paper. “The results of our study show that galectin-9 is turned on in astrocytes under inflammatory conditions and has the potential to kill autoimmune cells.”
Multiple sclerosis affects between 2 and 3 million people worldwide. It seems to affect women at least twice as often as men, and some studies now suggest it could be four times more prevalent in females.
Also, where a person lives seems to affect his or her odds of contracting the disease. The farther a person lives from the equator, the greater his or her chance of getting MS, and people in Scandinavian countries seem to be especially at risk. It usually strikes between the ages of 20 to 50, but in “recent years, there has been an increase in cases of pediatric MS, from age 10 and under,” Welsh, who has studied the disease for more than 25 years, notes.
“As for living far from the equator, some studies indicate that lack of UV light might be a factor in susceptibility to developing MS,” she adds. “We do know that a lack of vitamin D seems to increase the odds of contracting MS. The disease is influenced by certain factors such as viral infections, environmental factors and stress.”
The chances of getting MS are about 750 to 1, but if a parent or a sibling has the disease, the odds are greatly lowered to 1 in 100. It has struck some high-profile people through the years.
MS sufferers have included entertainers such as comedian Richard Pryor, talk show host Montel Williams, singers Alan Osmond of the Osmond Brothers and country’s Donna Fargo, actress Teri Garr, former NFL quarterback Roman Gabriel and FOX news commentator Neil Cavuto. Ann Romney, wife of presidential candidate Mitt Romney, said last year she has battled MS since 1998, and former Mouseketeer and actress Annette Funicello fought the disease the last 30 years of her life before dying in April.
There is no cure for MS. However, in recent years, several treatments have become available, and the most effective treatments are those that target the cells of the peripheral immune system, the researchers add.
“We now know that galectin-9 produced by the brain’s resident astrocytes can restrict the autoimmune cells in culture,” says Li, “but we need to learn more about what happens in the intact brain, and that is what we are currently working on.”
The researchers hope that a better understanding of interactions between the brain cells and the autoimmune cells may one day offer new therapeutic targets for attenuating MS.
The project was funded by research grants from the National Institutes of Health and the National Multiple Sclerosis Society. Steelman is supported by a fellowship from the National Multiple Sclerosis Society.
Press release courtesy of the University of Texas A&M.