Interleukin-4 induced 1 (IL4I1) promotes central nervous system remyelination

This scientific commentary refers to ‘IL4I1 augments CNS remyelination and axonal protection by modulating T cell driven inflammation’, by Psachoulia et al. (doi:10.1093/brain/aww254) .Multiple sclerosis is an inflammatory demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin sheaths and axons (Lorscheider et al. , 2016). Most patients initially develop relapsing-remitting disease (RRMS), in which acute neurological deficits are interspersed with periods of partial or complete recovery. However, up to 65% of patients with RRMS eventually develop secondary progressive multiple sclerosis (SPMS), in which disability increases continually. Conversion to SPMS is associated with a relatively poor prognosis, in part due to the limited effectiveness of disease-modifying therapies in the progressive phase (Lorscheider et al. , 2016). This in turn partly reflects the complex interactions between the multiple pathophysiological mechanisms responsible for demyelination and neurodegeneration. However, there is also compelling evidence that a decline in regenerative capacity occurs in the brain in chronic multiple sclerosis, possibly due to dysregulation of inflammation (Fitzner and Simons, 2010). Unravelling the mechanisms that link the immune system with CNS damage and repair therefore represents both a challenge and an opportunity for multiple sclerosis research.In this issue of Brain , Psachoulia et al. (2016) exploit a published remyelination transcriptome obtained from laser capture microdissected CNS lesions induced in the rodent CNS by lysolecithin/lysophosphatidylcholine (LPC) (Huang et al. , 2011), to identify novel markers of remyelination. Of the more than 8000 differentially regulated genes, Il4i1 , a phenylalanine oxidase secreted mainly by myeloid antigen presenting cells (APCs), was among the most strongly upregulated (4-fold increase at 14 days versus 5 days post-lesion). In situ hybridization demonstrated that Il4i1 was predominantly expressed in cells with morphology reminiscent of foamy macrophages, beginning as early as 10–14 days post-lesion, a …