Evidence map›Paper›PMID 40038877›Full record

ArticleClinical and translational medicine2025

Topical TYK2 inhibitor ameliorates psoriasis-like dermatitis via the AKT-SP1-NGFR-AP1 pathway in keratinocytes.

Zhiqin Fang, Rundong Jiang, Yutong Wang, Wangqing Chen, Xiang Chen, Mingzhu Yin

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Zhiqin FangDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Rundong JiangDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yutong WangDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wangqing ChenDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiang ChenDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Mingzhu YinDepartment of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0002-6964-7131

Funding

Chongqing Natural Science Foundation CSTB2023NSCQ-MSX0658Hunan Natural Science Foundation for Distinguished Young Scholars 2021JJ10073Hunan Provincial Natural Science Foundation 2024JJ5601National Key R&D Programs of China 2022YFC3601800The Natural Science Foundation of China General Program 82073020The Natural Science Foundation of China Youth Program 32200523
6 · The paper itself

Abstract

introductionTyrosine kinase 2 (TYK2)-dependent cytokine signalling is integral to the pathogenesis of psoriasis. While BMS-986165, a highly selective TYK2 inhibitor, has recently been approved for oral treatment of psoriasis, its therapeutic potential via topical application remains unexplored.

objectivesWe aim to investigate the efficacy of topically applying TYK2 inhibitor in psoriasis and to elucidate the underlying mechanisms driving the therapeutic effects of this delivery approach.

methods1.5% BMS-986165 ointment was applied topically to the back skin of imiquimod (IMQ)-induced psoriatic mice. To identify potential target cells influenced by the topical TYK2 inhibitor, we performed single cell RNA sequencing (scRNA-seq) and flow cytometry on mouse lesions. The role of TYK2 in vitro was assessed by silencing its expression or administering BMS-986165 in human keratinocytes (KCs). Mechanistic insights into TYK2 function in KCs were further investigated using RNA-seq, dual luciferase reporter assay and ChIP-qPCR.

resultsExternal use of 1.5% BMS-986165 ointment significantly ameliorated the IMQ-induced psoriasis-like dermatitis. Importantly, topical TYK2 inhibitor attenuated proinflammatory capability of KCs. In vitro, TYK2 inhibition suppressed the transcription of nerve growth factor receptor (NGFR) by disrupting the AKT-SP1 signalling pathway. This impairment hindered the activation of activator protein 1 (AP1), thereby weakening the proinflammatory potential of KCs.

conclusionThis study reveals a novel therapeutic potential for selective TYK2 inhibitor in topical manner on psoriasis therapy, which might prompt the development of topical treatment for psoriasis. Crucially, our findings provide an underexplored regulatory mechanism of TYK2 inhibitor in psoriasis. KEY POINTS: Topical TYK2 inhibitor alleviates psoriasis-like dermatitis. Topical TYK2 inhibitor reduces psoriasis progression through restraining the inflammatory responses of keratinocytes. The inhibition of TYK2 regulates the inflammatory response of keratinocytes through AKT-SP1-NGFR-AP1 pathway.

Indexed as

DermatitisKeratinocytesPsoriasisTYK2 KinaseAdministration, TopicalAnimalsDisease Models, AnimalHumansMiceProto-Oncogene Proteins c-aktSignal TransductionTranscription Factor AP-1Proto-Oncogene Proteins c-aktTranscription Factor AP-1TYK2 KinaseTYK2 protein, humaninflammatory responsekeratinocytepsoriasistopical treatmentTYK2 inhibitor

Identifiers

PMID40038877
PMCPMC11879890

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.