Targeting Cannabinoid 1 Receptor in Macrophages Alleviates Psoriatic Skin Inflammation Through the AUF1-NLRP3 Axis.
7 affiliations
- 1Department of Molecular Science & Technology, Ajou University, Suwon, Republic of Korea.
- 2Department of Medical Science, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
- 3Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
- 4Advanced College of Bio-Convergence Engineering, Ajou University, Suwon, Republic of Korea.
- 5Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
- 6National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
- 7Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Abstract
Psoriasis is a chronic inflammatory skin disease associated with systemic metabolic dysregulation; however, the molecular pathways linking metabolic signaling to skin inflammation remain poorly understood. Here, we identify cannabinoid 1 receptor (CB1R) in macrophages as a key immunometabolic regulator of psoriatic inflammation and a potential therapeutic target. CB1R expression was increased in macrophages infiltrating psoriatic lesional skin in both humans and mice, and both pharmacological inhibition and genetic deletion of CB1R markedly attenuated psoriasis-like pathology in mouse models by reducing epidermal hyperplasia, inflammation, and barrier dysfunction in a macrophage-dependent manner. Mechanistically, CB1R signaling in macrophages suppressed expression of the RNA-binding protein AUF1, leading to stabilization of Nlrp3 mRNA and enhanced NLRP3 inflammasome activation. AUF1 directly bound an AU-rich region within the Nlrp3 3' untranslated region and promoted mRNA destabilization, thereby limiting inflammasome activation and IL-1β production. Restoration of AUF1 expression, either by CB1R inhibition or overexpression, reduced NLRP3 levels and alleviated psoriasis-like pathology, whereas Nlrp3 deficiency abrogated these effects. Collectively, these findings define a CB1R-AUF1-NLRP3 signaling axis that links metabolic signaling to inflammasome-driven skin inflammation in macrophages. Targeting macrophage CB1R may therefore represent a promising therapeutic strategy for psoriasis and other immunometabolic inflammatory diseases.
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BibTeX
@article{choi2026targeting,
title = {{Targeting Cannabinoid 1 Receptor in Macrophages Alleviates Psoriatic Skin Inflammation Through the AUF1-NLRP3 Axis.}},
author = {Hongseo Choi and Sukyoung Han and Jinho Kim and Ji Hye Han and Eunsu Kim and Yeonjeong Heo and Minju Lee and Jooyoung Lee and Heerim You and Soyoun Lee and Su-Hee Han and Ilrok Yoon and Sung Anjeon and Hyerim Kang and Seungyeon Ryu and Hyun-Ji Park and Eunha Kim and Chul Hwan Bang and Ji Hyun Lee and Josephine M Egan and Jung-Woong Kim and Eun Kyung Lee and Wook Kim},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78313},
url = {https://europepmc.org/article/MED/42875876},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting Cannabinoid 1 Receptor in Macrophages Alleviates Psoriatic Skin Inflammation Through the AUF1-NLRP3 Axis.
AU - Hongseo Choi
AU - Sukyoung Han
AU - Jinho Kim
AU - Ji Hye Han
AU - Eunsu Kim
AU - Yeonjeong Heo
AU - Minju Lee
AU - Jooyoung Lee
AU - Heerim You
AU - Soyoun Lee
AU - Su-Hee Han
AU - Ilrok Yoon
AU - Sung Anjeon
AU - Hyerim Kang
AU - Seungyeon Ryu
AU - Hyun-Ji Park
AU - Eunha Kim
AU - Chul Hwan Bang
AU - Ji Hyun Lee
AU - Josephine M Egan
AU - Jung-Woong Kim
AU - Eun Kyung Lee
AU - Wook Kim
PY - 2026
DA - 2026/10/14
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78313
UR - https://europepmc.org/article/MED/42875876
AB - Psoriasis is a chronic inflammatory skin disease associated with systemic metabolic dysregulation; however, the molecular pathways linking metabolic signaling to skin inflammation remain poorly understood. Here, we identify cannabinoid 1 receptor (CB1R) in macrophages as a key immunometabolic regulator of psoriatic inflammation and a potential therapeutic target. CB1R expression was increased in macrophages infiltrating psoriatic lesional skin in both humans and mice, and both pharmacological inhibition and genetic deletion of CB1R markedly attenuated psoriasis-like pathology in mouse models by reducing epidermal hyperplasia, inflammation, and barrier dysfunction in a macrophage-dependent manner. Mechanistically, CB1R signaling in macrophages suppressed expression of the RNA-binding protein AUF1, leading to stabilization of Nlrp3 mRNA and enhanced NLRP3 inflammasome activation. AUF1 directly bound an AU-rich region within the Nlrp3 3' untranslated region and promoted mRNA destabilization, thereby limiting inflammasome activation and IL-1β production. Restoration of AUF1 expression, either by CB1R inhibition or overexpression, reduced NLRP3 levels and alleviated psoriasis-like pathology, whereas Nlrp3 deficiency abrogated these effects. Collectively, these findings define a CB1R-AUF1-NLRP3 signaling axis that links metabolic signaling to inflammasome-driven skin inflammation in macrophages. Targeting macrophage CB1R may therefore represent a promising therapeutic strategy for psoriasis and other immunometabolic inflammatory diseases.
SN - 2198-3844
ER -