FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Psoriatic Inflammation

Jianyu Yu; Jiaqing Hao; Matthew S. Yorek; Xingshan Jiang; Anthony Avellino; Shanshan Liu; Xiaochun Han; Jonathan Shilyansky; Zhaohua Wang; Yuhang Wang; Zizhen Kang; Ali Jabbari; Bing Li

doi:10.1016/j.celrep.2025.116254

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FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Psoriatic Inflammation

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FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Psoriatic Inflammation

Jianyu Yu, Jiaqing Hao, Matthew S. Yorek, Xingshan Jiang, Anthony Avellino, Shanshan Liu, Xiaochun Han, Jonathan Shilyansky, Zhaohua Wang, Yuhang Wang, …

Cell reports (Cambridge), Vol.44(9), 116254

09/05/2025

DOI: 10.1016/j.celrep.2025.116254

PMCID: PMC12516882

PMID: 40913763

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Abstract

High fat diet (HFD)-induced obesity increases the risk and severity of psoriasis. However, the immunoregulatory effects of different HFD-induced obesity on psoriasis pathogenesis remains poorly understood. Here, mimicking human dietary fat profiles, four HFDs ꟷ saturated, monounsaturated, omega-6 and omega-3 fats ꟷ were designed and used to induce obesity in mice. Despite comparable obesity levels across groups, only the saturated HFD exacerbated imiquimod (IMQ)-induced psoriasis. This exacerbation correlated with elevated levels of IL-1β-producing macrophages, IL-17A-producing γδ T cells, and neutrophils within psoriatic lesions. Mechanistically, saturated fatty acids (FAs) promoted IL-1β/IL-17A signaling via fatty acid-binding protein 5 (FABP5)-mediated mitochondrial FA oxidation and extracellular ATP release in skin macrophages. Deletion of FABP5, either globally or specifically in macrophages, attenuated IL-1β/IL-17A signaling and alleviated IMQ-induced psoriasis. These findings identify FABP5 as a key mediator of saturated HFD-driven psoriasis via the IL-1β/IL-17 axis, offering insights into the interplay between dietary fats, obesity and psoriasis. [Display omitted] •Saturated, but not unsaturated, HFDs exacerbate the development of psoriatic inflammation.•Saturated fats enhance IL-1β/IL-17A signaling in psoriatic skin.•FABP5 mediates saturated fat-induced IL-1β by promoting ATP production and signaling.•Deletion of FABP5 in macrophages alleviates saturated HFD-associated psoriasis. Yu et al. demonstrate that saturated high fat diets exacerbate psoriasis through FABP5-mediated fatty oxidation and extracellular ATP release, leading to enhanced IL-1β/IL17A signaling for skin inflammation.

FABP5

IL-1 β

IL-17

Macrophages

Psoriasis

Saturated fats

Details

Title: Subtitle: FABP5 in Skin Macrophages Mediates Saturated Fat-Induced IL-1β Signaling in Psoriatic Inflammation
Creators: Jianyu Yu - University of Iowa
Jiaqing Hao - University of Iowa
Matthew S. Yorek - University of Iowa
Xingshan Jiang - University of Iowa
Anthony Avellino - University of Iowa
Shanshan Liu - University of Iowa
Xiaochun Han - University of Iowa
Jonathan Shilyansky - University of Iowa, Pathology
Zhaohua Wang - University of Iowa
Yuhang Wang - University of Iowa
Zizhen Kang - University of Iowa
Ali Jabbari - University of Iowa
Bing Li - University of Iowa
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.44(9), 116254
DOI: 10.1016/j.celrep.2025.116254
PMID: 40913763
PMCID: PMC12516882
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Elsevier Inc
Grant note: NIH: R01AI137324, R01CA180986, U01CA272424
We thank the Department of Pathology at the University of Iowa for the access to use the Cytek Aurora flow cytometry. B.L. thanks the funding support from NIH grant nos. R01AI137324, R01CA180986, and U01CA272424.
Language: English
Date published: 09/05/2025
Academic Unit: Dermatology; Pathology; Iowa Neuroscience Institute; Surgery
Record Identifier: 9984962545202771

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