| First Author | Hao J | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 11 | Pages | 113449 |
| PubMed ID | 37967009 | Mgi Jnum | J:348585 |
| Mgi Id | MGI:7561370 | Doi | 10.1016/j.celrep.2023.113449 |
| Citation | Hao J, et al. (2023) Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis. Cell Rep 42(11):113449 |
| abstractText | One of the hallmarks of intractable psoriasis is neutrophil infiltration in skin lesions. However, detailed molecular mechanisms of neutrophil chemotaxis and activation remain unclear. Here, we demonstrate a significant upregulation of epidermal fatty acid binding protein (E-FABP, FABP5) in the skin of human psoriasis and psoriatic mouse models. Genetic deletion of FABP5 in mice by global knockout and keratinocyte conditional (Krt6a-Cre) knockout, but not myeloid cell conditional (LysM-Cre) knockout, attenuates psoriatic symptoms. Immunophenotypic analysis shows that FABP5 deficiency specifically reduces skin recruitment of Ly6G(+) neutrophils. Mechanistically, activated keratinocytes produce chemokines and cytokines that trigger neutrophil chemotaxis and activation in an FABP5-dependent manner. Proteomic analysis further identifies that FABP5 interacts with valosin-containing protein (VCP), a key player in NF-kappaB signaling activation. Silencing of FABP5, VCP, or both inhibits NF-kappaB/neutrophil chemotaxis signaling. Collectively, these data demonstrate dysregulated FABP5 as a molecular mechanism promoting NF-kappaB signaling and neutrophil infiltration in psoriasis pathogenesis. |
