Transcobalamin 2 and Psoriasis

[Fred]

Could a B12 delivery system Transcobalamin 2 (TCN2) be a new target for psoriasis ?

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Psoriasis is a chronic immune-mediated inflammatory disorder with systemic implications. While transcobalamin 2 (TCN2) has been linked to several autoimmune diseases, its role in psoriasis remains unclear. Here, we investigated the contribution of TCN2 to psoriatic pathogenesis.

TCN2 expression was significantly elevated in both lesional skin and peripheral blood mononuclear cells (PBMCs) from psoriasis patients, and its levels declined following biologic therapy. Similarly, increased TCN2 expression was observed in imiquimod (IMQ)-induced psoriatic lesions in mice. To further evaluate its function, we generated Tcn2-deficient (Tcn2−/−) mice and established an IMQ-induced psoriasis model. Compared with wild-type controls, Tcn2−/− mice developed attenuated skin lesions with reduced epidermal hyperplasia and inflammation.

Transcriptomic analysis of lesional skin revealed downregulation of inflammatory mediators (S100A7, S100A8, S100A9, IL-1β, IL-6) and suppression of STAT3 signaling in Tcn2−/− mice. In parallel, TCN2-knockdown HaCaT cells exhibited impaired proliferation due to G1-phase arrest, along with reduced expression of proinflammatory factors. Together, these findings demonstrate that TCN2 promotes keratinocyte hyperproliferation and amplifies inflammatory responses in psoriasis.

In conclusion, this study identifies TCN2 as a previously unrecognized regulator of psoriatic inflammation and keratinocyte biology, highlighting its potential as a novel therapeutic target.

Source: onlinelibrary.wiley.com

*Funding: National Natural Science Foundation of China. Elite Medical Professionals Project of China-Japan Friendship Hospital. National High Level Hospital Clinical Research Funding