Immunomodulatory Effect of Methotrexate Abruptly Controls Keratinocyte Activation in Psoriasis

Abstract

In psoriatic skin, epidermal keratinocytes (KCs) undergo deregulated inflammatory response that leads to prolonged expression of inflammatory mediators as well as abnormal keratins. Due to immune and genetic factors, KCs get activated and cell balance gets disturbed. This activation is mainly due to deregulated inflammatory response. A vicious cycle of KC-immune response called KC activation cycle leads to psoriasis. In psoriatic skin, epidermal KCs undergo deregulated inflammatory response that leads to prolonged expression of inflammatory mediators as well as abnormal keratins. Methotrexate (MTX) an immunosuppressive agent has been used as a standard drug to treat severe psoriasis. Acanthosis and abnormal terminal differentiation was mainly due to the mutation in epidermal keratins. In turn, disease severity and relapsing of psoriasis are mainly due to the mutation of hyperproliferative keratins. These novel keratin mutations in psoriatic epidermis might be one of the causative factors for psoriasis. MTX strongly regulates the KC activation cycle by deregulated inflammatory markers and maintains normal keratin phenotype on hyperproliferating KC, thereby controlling acanthosis in psoriasis patients.