A function of MOG in the regulation of the immune system

23 June 2014

BPRC - 1. A function of MOG in the regulation of the immune system

Myelin oligodendrocyte glycoprotein (MOG) is a specific component of the myelin sheath, a compact multi-lamellar structure that winds around axons in the central nervous system (CNS) and protects them against injury. The only well-established function of MOG is detrimental, as it is the primary target of autoimmune reactions against CNS myelin in the disease multiple sclerosis (MS). It is unlikely, however, that expression of MOG in such vulnerable organs as brain and spinal cord is tolerated when it would not have a relevant physiological role, although such function has not been documented thus far. BPRC scientists have contributed to the elucidation of this enigma by scientists from the Free University Medical Center in Amsterdam.

In a publication in the Journal of Experimental Medicine it is shown that MOG is the only ligand in myelin of DC-SIGN, an innate immune receptor expressed on human antigen presenting cells (APC), including microglia and dendritic cells (DC). Binding of MOG to DC-SIGN, which is mediated by the sugar moiety, keeps the APC in an anti-inflammatory tolerogenic state even in the presence of danger signals relayed by LPS binding to TLR4. However, under the influence of inflammation, the glycosylation of MOG is altered impairing binding to DC-SIGN, resulting in the maturation of DC to a pro-inflammatory and immunogenic APC.

The reported phenomenon may explain why myelin injury per se does not lead to an autoimmune disease against the CNS, while the combination of myelin injury with inflammation might underlie the progressively accumulating autoimmune attack on CNS myelin observed in MS.