SPNS1 deficiency alleviates the development of atopic dermatitis by suppressing keratinocyte proliferation

Mengjie Li^a,b,d,?, Guihong Liu^a,b,c,?, Kai Wang^a,b,d,?, Baoshan Tang^a,b, Yepeng Wu^a,b,c, Bo Chen^a,b,c, Junfei Jin^a,b,c, Fangru Chen^a,e,, Zhixiong Pan^a,b,c,d,

ABSTRACT: This study aimed to investigate the role of the protein SPNS1 in the pathogenesis of atopic dermatitis (AD) and the underlying mechanisms, with a particular focus on keratinocyte proliferation and lysosomal function. Analysis of GEO datasets revealed a significant upregulation of SPNS1 in lesional skin from AD patients and DNCB-induced mouse models. An AD-like mouse model was established by applying DNCB to SPNS1 heterozygous (SPNS1+/?) mice, and humankeratinocytes (HaCaT) were stimulated with IL-4/IL-13 following SPNS1 knockdown. Epidermal thickness and cell proliferation were assessed via H&E staining and Ki-67 immunofluorescence, while cell viability, apoptosis, and lysosomal morphology were evaluated using the CCK-8 assay, flow cytometry, and immunofluorescence, respectively. The results showed that SPNS1 deficiency alleviated AD-like skin inflammation and epidermal hyperplasia. Both in vivo and in vitro, SPNS1 knockdown suppressed keratinocyte hyperproliferation, induced G1/S cell cycle arrest, and promoted apoptosis. Moreover, SPNS1 deficiency disrupted lysosomal morphology and function. Clinically, effective ADtreatment was associated with downregulated SPNS1 expression. These findings demonstrate that SPNS1 promotes ADprogression by driving keratinocyte hyperproliferation, potentially through the disruption of lysosomal homeostasis, thereby positioning SPNS1 as a promising therapeutic target for AD.

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^a	Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001 China
^b	China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, Guangxi 541001 China
^c	Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001 China
^d	Clinical Laboratory Center, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541004 China
^e	Department of Dermatology, The First Affiliated Hospital of Guilin Medical University, Guangxi 541004 China

* Corresponding author, E-mail: chenfangru82@glmc.edu.cn, pzhix217@glmc.edu.cn

Received 24 Nov 2025, Accepted 9 Apr 2026

SPNS1 deficiency alleviates the development of atopic dermatitis by suppressing keratinocyte proliferation

Mengjie Lia,b,d,?, Guihong Liua,b,c,?, Kai Wanga,b,d,?, Baoshan Tanga,b, Yepeng Wua,b,c, Bo Chena,b,c, Junfei Jina,b,c, Fangru Chena,e,*, Zhixiong Pana,b,c,d,*

Mengjie Li^a,b,d,?, Guihong Liu^a,b,c,?, Kai Wang^a,b,d,?, Baoshan Tang^a,b, Yepeng Wu^a,b,c, Bo Chen^a,b,c, Junfei Jin^a,b,c, Fangru Chen^a,e,, Zhixiong Pan^a,b,c,d,