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ResearchIn-Press PreviewDermatologyMetabolism Open Access | 10.1172/jci.insight.203626

Type 3 Inflammation-Specific Keratinocyte Glutaminolysis Promotes Skin Inflammation

Yongfei Hu,1 Hai Yu,2 Kaiyu Liang,1 Liyan Yuan,1 Wenjun Zhang,1 Zhe Zhuang,1 Suyun Ji,1 and Xichun Xia1

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Hu, Y. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Yu, H. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Liang, K. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Yuan, L. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Zhang, W. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Zhuang, Z. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Ji, S. in: PubMed | Google Scholar

1Institute of Dermatology and Venereology, Southern Medical University, Guangzhou, China

2Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Find articles by Xia, X. in: PubMed | Google Scholar

Published September 8, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.203626.
Copyright © 2026, Hu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 8, 2026 - Version history
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Abstract

Inflammatory cytokines reprogram keratinocyte metabolism, but the metabolic pathways that couple immune signals to pathological epidermal growth remain incompletely defined. Here, we identify GLS1-mediated glutaminolysis as a metabolic program preferentially induced in keratinocytes under type 3 inflammatory conditions. Integrated transcriptomic, metabolomic, genetic, and functional analyses showed that IL-17A induced GLS1 expression and glutaminolysis in keratinocytes. Keratinocyte-specific Gls1 deletion reduced the intracellular availability of arginine, proline, and methionine, impaired amino acid-dependent mTORC1 activation, disrupted redox homeostasis, and limited keratinocyte proliferation. Amino acid or antioxidant supplementation partially rescued these defects, whereas rapamycin blocked the amino acid-mediated proliferative rescue. Gls1 deletion did not impair steady-state skin development or homeostasis and did not alter MC903-induced type 2 dermatitis, but it delayed wound re-epithelialization and attenuated IMQ-induced psoriasiform inflammation. Loss of keratinocyte GLS1 also reduced epidermal chemokine expression and the accumulation of neutrophils and IL-17A-producing γδ T cells, revealing a role for glutaminolysis in amplifying epithelial-immune crosstalk. These findings define GLS1-mediated glutaminolysis as a context-specific metabolic checkpoint linking type 3 inflammation to keratinocyte proliferation and cutaneous immune amplification, and support locally or temporally controlled GLS1 inhibition as a potential therapeutic strategy for psoriasis.

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  • Version 1 (September 8, 2026): In-Press Preview
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