Lipocalin-2 as a mediator of neuroimmune communication

J Leukoc Biol. 2023 Dec 27:qiad157. doi: 10.1093/jleuko/qiad157. Online ahead of print.


Lipocalin-2 (LCN2), a neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa secreted protein implicated in a broad range of inflammatory diseases affecting the brain and periphery. It is a pleotropic protein expressed by various immune and non-immune cells throughout the body. Importantly, the surge in LCN2 levels in disease states has been associated with a myriad of undesirable effects, further exacerbating the ongoing pathological processes. In the brain, glial cells are the principal source of LCN2, which plays a definitive role in determining their functional phenotypes. In different central nervous system (CNS) pathologies, an increased expression of glial LCN2 has been linked to neurotoxicity. LCN2 mediates a crosstalk between central and peripheral immune cells under neuroinflammatory conditions. One intriguing aspect is that elevated LCN2 levels in peripheral disorders, such as cancer, metabolic conditions, and liver diseases, potentially incite an inflammatory activation of glial cells while disrupting neuronal functions. This review comprehensively summarizes the influence of LCN2 on the exacerbation of neuroinflammation by regulating various cellular processes. Additionally, this review explores LCN2 as a mediator of neuroimmune crosstalk in various CNS pathologies and highlights the role of LCN2 in carrying inflammatory signals along the neuroimmune axis.

Keywords: astrocytes; lipocalin-2; microglia; neuroimmune axis; neuroinflammation; peripheral diseases.