SIRT6 Aggravates Psoriasiform Skin Inflammation Through Modulation of the SOCS2-STAT1/3 Pathway
Mingjie He1, Qing Guo1, Xiaofang Wang2
1Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Journal of Inflammation Research
|August 11, 2026
Summary
SIRT6 (sirtuin 6) exacerbates psoriasis by activating the SOCS2-STAT1/3 pathway. Topical SIRT6 inhibition shows therapeutic potential for psoriasis treatment.
Area of Science:
- Dermatology
- Molecular Biology
- Biochemistry
Background:
- Psoriasis is a chronic inflammatory skin disease.
- The role of sirtuin 6 (SIRT6) in psoriasis pathogenesis is not fully understood.
- SIRT6 is a deacetylase with potential roles in inflammation and cell signaling.
Purpose of the Study:
- To investigate the role of SIRT6 in psoriasis.
- To elucidate the molecular mechanisms underlying SIRT6's function in psoriasis.
- To evaluate SIRT6 as a therapeutic target for topical psoriasis treatment.
Main Methods:
- Analyzed SIRT6 expression in psoriatic lesions and healthy skin using GEO datasets.
- Established a psoriasis-like cellular model using TNF-α stimulated HaCaT cells.
- Investigated SIRT6's effects on keratinocyte inflammation, proliferation, and migration via overexpression and knockdown.
- Utilized transcriptomic analysis to identify SIRT6-regulated pathways.
- Assessed therapeutic potential using a SIRT6 inhibitor-loaded hydrogel in mouse models and human skin explants.
Main Results:
- SIRT6 expression is significantly elevated in psoriatic lesions compared to healthy skin.
- SIRT6 overexpression in keratinocytes enhanced inflammation, proliferation, and migration.
- SIRT6 activates the STAT signaling pathway by downregulating SOCS2 and upregulating STAT1/3 phosphorylation.
- Topical SIRT6 inhibition with a hydrogel alleviated psoriasiform dermatitis in mice and reduced inflammation in human psoriatic skin explants.
Conclusions:
- SIRT6 exacerbates psoriasiform inflammation through the SOCS2-STAT1/3 signaling pathway.
- Topical inhibition of SIRT6 presents a promising therapeutic strategy for psoriasis.
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