CEACAM5 drives psoriatic inflammation by regulating CD8⁺ T cell recruitment and activation

As a chronic relapsing immune-mediated skin disorder, psoriasis is mainly driven by CD8⁺ T cells during disease progression, while the molecular basis of CD8⁺ T cell recruitment and activation in psoriatic lesions remains largely unclear, and the function of CEACAM5 in psoriasis remains uncharacterized. Here, we report that CEACAM5 is significantly upregulated in psoriatic patient epidermal lesions and M5-induced psoriatic keratinocytes in vitro. CEACAM5 knockdown prominently inhibits chemokine expression in keratinocytes, attenuates CD8⁺ T cell recruitment, and downregulates pro-inflammatory cytokine production in recruited CD8⁺ T cells. Mechanistic studies reveal that soluble CEACAM5 directly activates the Lck/ZAP70 signaling axis to promote the inflammatory activation of CD8⁺ T cells. Collectively, our work identifies CEACAM5 as a critical regulator of CD8⁺ T cell responses in psoriasis, providing a novel potential therapeutic target for this disease.