Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis

Summary: 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...

Täydet tiedot

Bibliografiset tiedot
Päätekijät: Jiaqing Hao, Jianyu Yu, Matthew S. Yorek, Chi-Li Yu, R. Marshall Pope, Michael S. Chimenti, Yiqin Xiong, Aloysius Klingelhutz, Ali Jabbari, Bing Li
Aineistotyyppi: Artikkeli
Kieli:English
Julkaistu: Elsevier 2023-11-01
Sarja:Cell Reports
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Linkit:http://www.sciencedirect.com/science/article/pii/S2211124723014614
Kuvaus
Yhteenveto:Summary: 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-κB signaling activation. Silencing of FABP5, VCP, or both inhibits NF-κB/neutrophil chemotaxis signaling. Collectively, these data demonstrate dysregulated FABP5 as a molecular mechanism promoting NF-κB signaling and neutrophil infiltration in psoriasis pathogenesis.
ISSN:2211-1247