Reappraisal of psoriasis pathogenesis: the role of TEAD4 expression in keratinocytes.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disorder with a multifaceted pathogenesis. Immune dysregulation and immune cell dysfunction are among the mechanisms involved. TEA domain family member 4 (TEAD4) is suggested to play a role in psoriasis development. TEAD4 expression in keratinocytes may have a chemotactic effect and could disturb the function of FOXP3-positive T lymphocytes. This study aimed to evaluate the expressions of TEAD4 and FOXP3 in lesional, nonlesional psoriatic, and healthy skin and assess the clinical impact of their expression.

METHODS: This case-control study included 32 cases with psoriasis vulgaris and 32 control groups. Hematoxylin and eosin-stained slides were examined to evaluate the histopathological findings. Moreover, other sections were immunohistochemically stained with FOXP3 and TEAD4.

RESULTS: FOXP3 was expressed in inflammatory cells in 56.5, 37.5, and 12.5% of lesional, nonlesional, and healthy skin, whereas it was entirely negative in the keratinocytes. TEAD4 was expressed in keratinocytes in 93.7 and 46.9% of lesional and nonlesional skin, while negative in healthy skin. Significant differences were observed between their lesional, nonlesional, and healthy skin expressions. Furthermore, FOXP3 expression in lesional skin was significantly associated with early onset (P = 0.016), low PASI score (P = 0.002), mild psoriasis (P = 0.007), and axial affection (P = 0.022), while TEAD4 expression was associated with progressive course (P = 0.032), high PASI score (P = 0.002), severe psoriasis (P = 0.001), severe inflammation (P = 0.001), and progressive course (P = 0.017).

CONCLUSION: TEAD4 expression was higher in lesional than nonlesional skin and absent in healthy skin, suggesting a role in psoriasis development. TEAD4 expression was also associated with severe and progressive psoriasis. This may be mediated by the downregulation of FOXP3 and dysfunction of Treg cells. TEAD4 could serve as a promising therapeutic target in psoriasis.