RIPK1 downregulation enhances neutrophil extracellular
traps in psoriasis

Xinyu Meng; Ruru Guo; Chaofan Fan; Yixuan Li; Xuesong Liu; Xiaoxiang Chen; Liangjing Lu

doi:10.5114/ada.2022.113803

eISSN: 2299-0046
ISSN: 1642-395X

Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii

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abstract:

Original paper

RIPK1 downregulation enhances neutrophil extracellular traps in psoriasis

Xinyu Meng

¹

,

Ruru Guo

¹

,

Chaofan Fan

¹

,

Yixuan Li

¹

,

Xuesong Liu

^{1, 2}

,

Xiaoxiang Chen

¹

,

Liangjing Lu

¹

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Adv Dermatol Allergol 2022; XXXIX (1): 72-80

DOI: https://doi.org/10.5114/ada.2022.113803

Online publish date: 2022/02/28

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Introduction
Psoriasis is an immune-mediated systemic disease. Neutrophils are enriched in psoriasis lesions and can form neutrophil extracellular traps (NETs) to activate keratinocytes. Receptor-interacting protein kinase RIPK1 and RIPK3 are involved in necroptosis and NET formation.

Aim
To elucidate whether RIPK1 regulates circulating neutrophils to form NETs and inflammation in psoriasis.

Material and methods
Blood samples of psoriasis patients (n = 20) and healthy controls (n = 20) were detected by flow cytometry. The expression level of RIPK1/3 in isolated circulating neutrophils from psoriasis patients (n = 17) and healthy controls (n = 17) was examined by quantitative real-time PCR. SYTOX Green dye and PicoGreen reagent were used to detect NET formation and DNA release in neutrophils under the stimulation of phorbol 12-myristate 13-acetate (PMA) and necrostain-1 (Nec-1). Correlation analysis was performed between RIPK1/3 expression and Psoriasis Area Severity Index (PASI), neutrophil-to-lymphocyte ratio (NLR).

Results
RIPK1 and RIPK3 expression in protein levels were decreased in monocytes and neutrophils from peripheral blood of psoriasis patients. In isolated psoriasis neutrophils, RIPK1 and Caspase8 mRNA were downregulated while RIPK3 and MLKL mRNA were elevated, leading to the necroptosis pathway. In addition, RIPK1-inhitor-necrostatin-1 (Nec-1) enhanced NETosis in psoriasis neutrophils in vitro. More importantly, there is a negative correlation between RIPK1 and psoriasis disease severity.

Conclusions
Our data demonstrated that downregulated RIPK1 expression in psoriasis neutrophils may enhance NET generation. RIPK1 may be identified as a novel therapeutic target in psoriasis.

keywords:

RIPK1 downregulation enhances neutrophil extracellular traps in psoriasis

Xinyu Meng 1 , Ruru Guo 1 , Chaofan Fan 1 , Yixuan Li 1 , Xuesong Liu 1, 2 , Xiaoxiang Chen 1 , Liangjing Lu 1

receptor-interacting protein kinase RIPK1, neutrophil, neutrophil extracellular traps, psoriasis

Xinyu Meng

¹

,

Ruru Guo

¹

,

Chaofan Fan

¹

,

Yixuan Li

¹

,

Xuesong Liu

^{1, 2}

,

Xiaoxiang Chen

¹

,

Liangjing Lu

¹