Topical histone deacetylase 1 inhibitor Entinostat ameliorates psoriasiform dermatitis through suppression of IL-17A response.

BACKGROUND

Biologics against IL-17A, IL-23 and TNF-α achieve a great success in treating psoriasis. However, the majority of patients still have some residual lesions left and require combination therapy to reach complete clearance. Topical medicine is an optional choice but only has limited categories. Besides, drug resistance is very often. Thus, topical medicine targeting new signaling pathway is still in an urgent need in the biologics era.

OBJECTIVE

To investigate the role of topical Entinostat, a selective inhibitor of histone deacetylases 1 (HDAC1) that has been tested in clinic trials to treat solid tumors and hematological malignancies, in psoriasis therapy.

METHODS

Efficacious Entinostat were tested in a mouse imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) model. An in vitro model consisting of human CD4 + T cell, murine T cells and NHEKs were used to screen Entinostat for inhibition of cutaneous inflammatory genes.

RESULTS

Topical application of Entinostat significantly improved psoriasiform inflammation in imiquimod-induced mice model with great reduction of IL-17A+ γδT cell infiltration in skin. Entinostat is powerful agent in inhibition of Th17 cell generation and the expression of psoriasis-related inflammatory mediators by primary keratinocytes upon CD4+ T cells stimulation.

CONCLUSION

Our findings suggest Entinostat is a promising topical medicine for psoriasis treatment.