A new study from The Weizmann Institute of Science, Israel, found that the inflammatory molecule CXCL12 promotes neuronal repair during spontaneous remission in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS).

The chemokine CXCL12 was previously thought to be a pro-inflammatory molecule only. But recent findings have shown that — depending on interactions with other factors, as well as the interactions’ timing and context — CXCL12 could also be anti-inflammatory and immunomodulating, and promote re-myelination.

The research team induced EAE in the mice and tracked the expression of CXCL12 in their brains, both during disease development and in the period of spontaneous remission. Researchers observed that levels of the molecule increased steadily while the disease advanced, and did not subside when the mice spontaneously recovered. Instead, the team found that the levels of the immune factor increased even further, even though inflammation was no longer present in the brain. The levels of CXCL12 in mice recovering from EAE were found to be significantly higher than in mice that had not experienced inflammation.

The spontaneous remission process was also accompanied by increased numbers of two cell types destined to turn into either new neurons or oligodendrocyte cells. Oligodendrocytes are the main myelin producing cells in the brain. A closer investigation of these cells showed that they were a source of CXCL12 and its receptor CXCR4.

The results highlighted the complexity of the immune response, showing that increased levels of immune molecules do not always contribute to pathology, but might be elevated to protect tissue, or — as in this case — triggering re-myelination and neuronal repair following inflammation.

The findings offer an important insight into healing processes in the brain, which might be explored in further studies aiming to develop new MS treatments.

The study, “Post-CNS-inflammation expression of CXCL12 promotes the endogenous myelin/neuronal repair capacity following spontaneous recovery from multiple sclerosis-like disease,” was led by Rina Zilkha-Falb from Sheba Medical Center and colleagues from The Weizmann Institute of Science, both in Israel, and the Ludwig-Maximilians-University, Munich, Germany. It was published online in the Journal of Neuroinflammation.