
건선 비병변부 및 세마포린 4A 결손 마우스에서 관찰되는 각질형성세포의 증식과 분화 이상, 그리고 T17 세포 침윤 증가는 건선 발병의 주요 기전을 나타낸다.


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Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown. Here, we revealed that while Sema4A expression was pronounced in psoriatic blood lymphocytes and monocytes, it was downregulated in the keratinocytes of both psoriatic lesions and non-lesions compared to controls. Imiquimod application induced more severe dermatitis in Sema4A knockout (KO) mice compared to wild-type (WT) mice. The naïve skin of Sema4AKO mice showed increased T cell infiltration and IL-17A expression along with thicker epidermis and distinct cytokeratin expression compared to WT mice, which are hallmarks of psoriatic non-lesions. Analysis of bone marrow chimeric mice suggested that Sema4A expression in keratinocytes plays a regulatory role in imiquimod-induced dermatitis. The epidermis of psoriatic non-lesion and Sema4AKO mice demonstrated mTOR complex 1 upregulation, and the application of mTOR inhibitors reversed the skewed expression of cytokeratins in Sema4AKO mice. Conclusively, Sema4A-mediated signaling cascades can be triggers for psoriasis and targets in the treatment and prevention of psoriasis.

### Competing Interest Statement

The authors have declared no competing interest.

Downregulation of Semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis

건선-비병변부의-특성을-반영하는-케라티노사이트의-세마포린-4a-발현-감소


건선 비병변부의 특성을 반영하는 케라티노사이트의 세마포린 4A 발현 감소
