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Updated: Apr 9, 2026
Murine Model of Epicutaneously-Induced Immunomodulation
Published on: June 24, 2025
DUSP6 Regulates Skin Inflammation, Parakeratosis and Disease Severity in a Murine Model of Psoriasis
Teresina Laragione1, Carolyn Harris1, Robert Phelps2
1Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract:
Psoriasis is a chronic inflammatory skin disease characterised by keratinocyte hyperproliferation and immune cell infiltration driven by cytokines such as IL-17A. The dual-specificity phosphatase 6 (DUSP6) is a negative regulator of MAPK signalling and was previously reported to be a key mediator of arthritis severity. Here, we examine the role of DUSP6 in a mouse model of psoriasis. Psoriasis was studied in the imiquimod-induced model (IMQ). The skin of DUSP6+/+ and DUSP6-/- mice was treated with IMQ cream. Disease severity was assessed using well-established clinical and histologic systems. Skin inflammatory genes were quantified by qPCR.DUSP6-/- mice exhibited significantly reduced skin inflammation with lower PASI clinical scores (mean DUSP6-/- 1.8 and DUSP6+/+ 8.4; p < 0.0001). Histologic scores for epidermal thickening, parakeratosis and immune cell infiltration were decreased in the DUSP6-/- mice (p < 0.0005), and mRNA levels of IL1β, IL17A and STAT3 were lower in DUSP6-/- skin (p ≤ 0.05) compared with DUSP6+/+. In conclusion, DUSP6 is required for the development of psoriasis-like skin inflammation in mice. In the absence of DUSP6, mice were protected and had significantly lower levels of pathogenic genes, suggesting a new and central role for DUSP6 in skin inflammation and a potential therapeutic target in psoriasis.
Insights
Dual-specificity phosphatase 6 (DUSP6) deficiency significantly reduces psoriasis-like skin inflammation in mice. Absence of DUSP6 protects against disease, highlighting its central role in skin inflammation and potential as a therapeutic target.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Psoriasis is a chronic inflammatory skin condition driven by keratinocyte hyperproliferation and immune cell infiltration.
- Cytokines like IL-17A are key drivers of psoriasis pathogenesis.
- Dual-specificity phosphatase 6 (DUSP6) negatively regulates MAPK signaling and is implicated in inflammatory diseases.
Purpose of the Study:
- To investigate the role of DUSP6 in a mouse model of psoriasis.
- To determine if DUSP6 deficiency impacts the development of imiquimod-induced psoriasis-like skin inflammation.
Main Methods:
- Utilized the imiquimod (IMQ)-induced mouse model of psoriasis.
- Compared disease severity in DUSP6+/+ (wild-type) and DUSP6-/- (knockout) mice.
- Assessed clinical and histological scores, and quantified inflammatory gene expression (IL1β, IL17A, STAT3) via qPCR.
Main Results:
- DUSP6-/- mice exhibited significantly reduced skin inflammation and lower Psoriasis Area and Severity Index (PASI) scores compared to DUSP6+/+ mice.
- Histological analysis revealed decreased epidermal thickening, parakeratosis, and immune cell infiltration in DUSP6-/- mice.
- mRNA levels of key inflammatory genes, including IL1β, IL17A, and STAT3, were significantly lower in the skin of DUSP6-/- mice.
Conclusions:
- DUSP6 is essential for the development of psoriasis-like skin inflammation in the IMQ mouse model.
- Absence of DUSP6 confers protection against skin inflammation, with reduced pathogenic gene expression.
- DUSP6 plays a central role in skin inflammation and represents a potential therapeutic target for psoriasis treatment.
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