Lipocalin 2 as a modulator of neuroinflammation and the blood-brain barrier

Lipocalin 2 (LCN2) is a small secreted protein that is expressed in a variety of diseases in different organ systems.

The expression of LCN2 is increased in the serum and cerebrospinal fluid of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS), and can be detected in MS lesions in the brain. Intrathecal production of LCN2 has been found mainly in patients with progressive MS and is lower in patients treated with natalizumab. Several important aspects of the inflammatory development and progression of MS lesions have been reported to be regulated by LCN2. These include the breakdown of the blood-brain barrier (BBB), the repair of myelin sheaths (remyelination) and the polarisation of microglia/monocytes towards a pro-inflammatory (M1) phenotype. In addition, LCN2 promotes the migration of astrocytes towards injured tissue by inducing chemokines such as CXCL10.

We have shown in previous research that LCN2 is mainly expressed by infiltrating monocytes and astrocytes in the autoimmune MS animal model EAE.

In this project, we are now investigating the role of LCN2 in lesion development and progression, as well as the intracellular signalling pathways and receptors for LCN2 under inflammatory conditions in the CNS.