Mechanism responsible for chronic inflammation in multiple sclerosis discovered!

Mechanism responsible for chronic inflammation in multiple sclerosis discovered!

Multiple sclerosis (MS) is an autoimmune disease. The defense system that usually protects patients from external aggression turns on its own cells and attacks them for reasons that are not yet known. Scientists  have shown that ancient viruses are involved in the acute inflammatory defense response that may contribute to the disease.

Multiple sclerosis (MS) is an incurable inflammatory autoimmune disease that leads to irreversible damage to the brain and spinal cord. This disease is also associated with the reactivation of ancient viruses, which were inserted in our DNA during the evolution of humankind. It was therefore long thought that multiple sclerosis was due to a viral infection.

"Our study shows that reactivation of ancient viruses does not correspond to an infectious phenomenon, but to a defense response of the body when faced with an acute inflammatory phenomenon" explains the senior author.

Viral sequences were neutralized during evolution and no longer represent a source of infection. But these sequences are a source of external DNA containing information about virus behavior. Cells have therefore been able to control these sequences to detect infections as quickly as possible and turn on their defense genes during an attack.

These viral sequences are, above all, used to control defense genes in stem cells. They lie dormant in adult cells and it is the more traditional sequences that become active. By examining samples from patients with MS, the scientists observed that regulatory sequences of viral origin emerged from their dormant state and were responsible for abnormal expression of several pro-inflammatory genes.

By exposing T cells to the pesticide dieldrin, the authors further found that a series of transcription of endogenous retroviruses (HERV)‐driven enhancers otherwise active only at stem cell stages can be reactivated by stress. This in part relies on peptidylarginine deiminase activity, possibly participating in the reawakening of silenced enhancers.

Likewise, usage of HERV‐driven enhancers was increased in myelin‐reactive T cells from patients with MS, correlating with activation of nearby genes at several sites. To conclude, in multiple sclerosis, activation of viral sequences does not correspond to an infectious phenomenon but to the unexpected use of regulatory sequences, leading to chronic excessive inflammation.

"The discovery of this mechanism, linked to epigenetic phenomena, may one day pave the way for management of MS using small molecules that inhibit chromatin modification enzymes" sums up the senior author.