Lipocalin 2 Participates in the Epidermal Differentiation and Inflammatory Processes of Psoriasis

As a multifunctional cytokine, lipocalin 2 is weakly expressed in skin and serum under normal conditions. However, it is over-expressed by neutrophils and keratinocytes in the skin lesions and sera in several skin diseases. Recent studies demonstrated that lipocalin 2 participates in the pathogenesis of psoriasis by exerting versatile effects on skin resident cells and infiltrating immune cells. Lipocalin 2 inhibits the synthesis of keratin, involucrin, and loricrin in keratinocytes, leading to epidermal parakeratosis via the Tcf7l1-lipocalin 2 signaling axis. It also recruits inflammatory cells such as T cells and neutrophils into skin lesions via the IL-23/IL17, p38-MAPK, and ERK-1/2 signaling pathways. Additionally, lipocalin 2 and other cytokines such as IL-17 have the synergetic effects on skin cells. The neutralization of lipocalin 2 or relevant cytokines can alleviate psoriasis, verifying that lipocalin 2 is an effective interfering target for psoriasis. In this review, we summarize the roles of lipocalin 2 in the processes of psoriatic inflammation and the promising therapeutic strategies based on lipocalin 2-related molecules.