One of the chief instigators of multiple sclerosis (MS) has a split personality. Immune cells known as microglia usually protect the nervous system, but when things go wrong, they strip neurons of myelin--their protective coating--leading to muscle spasms and memory difficulties. Now researchers have uncovered new clues into what turns these cellular Dr. Jekylls into Mr. Hydes.
When good microglia go bad, it's usually because of a protein called interferon gamma (IFN-gamma). Produced by the body's T-cells, IFN-gamma stimulates microglia to produce a myelin-damaging protein called tumor necrosis factor alpha (TNF-alpha).
To see if microglia could be turned away from the dark side, neuroimmunologist Michal Schwartz of the Weizmann Institute of Science, in Rehovet, Israel, examined mouse and rat models of MS. When the researchers looked at the response of microglia in these animals to various levels of IFN-gamma and a related protein, interleukin-4 (IL-4), they found that only high levels of IFN-gamma trigger microglia's damaging rampages. When IFN-gamma is low, microglia protect neurons just fine. And when IL-4 is around, it overcomes the malicious effects of IFN-gamma and TNF-alpha, switching microglia from nasty to nurturing. Under these conditions, microglia encourage the cells that make myelin, called oligodendrocytes, to repair damaged neurons.
It's too early to say whether microglia respond in exactly the same way in humans, but Schwartz hopes the findings will increase understanding of how MS progresses. The team reports its results online today in the Journal of Clinical Investigation.
It's "a very nice study" and a good demonstration of how microglia can be both good and bad for the nervous system, says neuropathologist Bill Blakemore of the University of Cambridge in the United Kingdom. He adds that more work will be needed to see how this could be applied to MS, as microglia are not the only cells in the immune system that have a two-faced personality.
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