Pathogenesis of psoriasis and development of treatment

Abstract The pathogenesis of psoriasis can be explained by dysregulation of immunological cell function as well as keratinocyte proliferation/differentiation. Recently, the immunological pathomechanism has been clarified substantially. Whereas T‐helper (Th)1 overactivation was thought to induce occurrence of psoriasis, it has been demonstrated that Th17 cells play a key role. Th17 development is maintained by interleukin ( IL )‐23 mainly produced by dendritic cells. Th17 cells produce various cytokines, including IL ‐17A, IL ‐17F and IL ‐22. IL ‐17A and IL ‐22 induce not only keratinocyte proliferation, but also tumor necrosis factor ( TNF )‐α, chemokine (C‐X‐C motif) ligand ( CXCL )1 and CXCL 8 production. TNF ‐α accelerates the infiltration of inflammatory cells, including lymphocytes, monocytes and neutrophils, from the peripheral blood into skin with dendritic cell activation. In addition, antimicrobial peptides are overexpressed in psoriatic skin lesions, and the antimicrobial peptide, LL ‐37, activates dendritic cells, which leads to the development of inflammation. Furthermore, activation of nuclear factor‐κB signal induces the expression of keratins 6 and 16 in keratinocytes, which are associated with acanthosis and reduced turnover time in the epidermis. The progression of the pathomechanism contributes to the development of new therapies for psoriasis.