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Increased neutrophil-derived IL-17A identified in generalized pustular psoriasis
Yu Lan1, Xiaoyan Wu2, Xinyu Zhong1
1Department of Dermatology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
Experimental Dermatology
|February 28, 2024
Summary
Generalized pustular psoriasis (GPP) involves neutrophil-derived IL-17A, distinct from psoriasis vulgaris. Targeting this pathway offers a potential GPP treatment, regardless of IL36RN mutations.
Area of Science:
- Dermatology
- Immunology
- Genetics
Background:
- Generalized pustular psoriasis (GPP) is a distinct inflammatory skin condition.
- Its pathogenesis, particularly in patients with interleukin (IL)36RN mutations, remains unclear.
- Psoriasis vulgaris (PV) serves as a comparative model for understanding GPP.
Purpose of the Study:
- To investigate the molecular differences between GPP and PV.
- To explore the role of IL-17A and IL-36 pathways in GPP pathogenesis.
- To identify potential therapeutic targets for GPP.
Main Methods:
- RNA sequencing of skin lesions from GPP and PV patients.
- Analysis of gene expression related to inflammation and neutrophil infiltration.
- Immunofluorescence staining to determine the cellular origin of IL-17A.
Main Results:
- GPP skin lesions showed overexpression of IL-17 signalling pathway genes and neutrophil-associated genes compared to PV.
- Patients with GPP and IL36RN mutations exhibited WNT11 upregulation and IL36RN downregulation.
- IL-17A in GPP skin lesions was predominantly derived from neutrophils, not T cells.
Conclusions:
- Neutrophil-derived IL-17A plays a crucial role in GPP pathogenesis, irrespective of IL36RN mutation status.
- Targeting neutrophil-derived IL-17A presents a promising therapeutic strategy for GPP.
