Protein Kinase CK2 Promotes Proliferation, Abnormal Differentiation, and Proinflammatory Cytokine Production of Keratinocytes via Regulation of STAT3 and Akt Pathways in Psoriasis

Protein kinase CK2 is a constitutively active and ubiquitously expressed serine/threonine kinase that is closely associated with various types of cancers, autoimmune disorders, and inflammation. However, the role of CK2 in psoriasis remains unknown. Herein, the study indicated elevated expression of CK2 in skin lesions from patients with psoriasis and from psoriasis-like mice. In the psoriasis-like mouse model, the CK2-specific inhibitor CX-4945 ameliorated imiquimod-induced psoriasis symptoms with reduced proliferation, abnormal differentiation, inflammatory cytokine production (especially IL-17A) of keratinocytes, and infiltration of gamma delta T cells. In in vitro studies, exogenous CK2 promoted hyper -proliferation and abnormal differentiation of human keratinocytes, which were reversed by the sup-pression of CK2 with CX-4945 or siRNA. Furthermore, knockdown of CK2 reduced IL-17A expression and abolished IL-17A-induced proliferation and inflammatory cytokine expression in keratinocytes. Interestingly, IL-17A increased the expression of CK2 in keratinocytes, thereby establishing a positive feedback loop. In addition, suppression of CK2 inhibited the activation of STAT3 and Akt signaling pathways in human keratinocytes and imiquimod-induced psoriatic lesions of mice. These findings indicate that a highly expressed CK2 level in the skin lesions is required in the development of psoriasis by promoting epidermal hyperplasia, abnormal differentiation, and inflammatory response via regula-tion of the STAT3 and Akt signaling pathways. CK2 may be a target for the treatment of psoriasis. (Am J Pathol 2023, 193: 567-578; https://doi.org/10.1016/j.ajpath.2023.01.016)

Automated summary

The study reveals that protein kinase CK2 is highly expressed in skin lesions of psoriasis patients and psoriasis-like mice. Inhibition of CK2 can alleviate psoriasis symptoms by reducing epidermal hyperplasia, abnormal differentiation, inflammatory cytokine production, and T cell infiltration. CK2 overexpression promotes hyper-proliferation and abnormal differentiation of keratinocytes, while its suppression reverses these effects. CK2 knockdown reduces IL-17A expression and inhibits IL-17A-induced proliferation and inflammatory response. Additionally, CK2 inhibition suppresses the activation of STAT3 and Akt signaling pathways. Therefore, CK2 may be a potential target for psoriasis treatment.