The Relapse of Psoriasis: Mechanisms and Mysteries

One-year safety and efficacy of tapinarof cream for the treatment of plaque psoriasis: Results from the PSOARING 3 trial

“…4 Furthermore, psoriasis can recur after cessation of therapy, including corticosteroids or biologics. 4,5 No topicals with novel mechanisms of action had been approved by the Food and Drug Administration (FDA) for over 25 years, highlighting a need for efficacious topical therapies that address these limitations. 1,4 Tapinarof (VTAMA Ò ; Dermavant Sciences, Inc) is a novel, first-in-class, small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) agonist, FDA approved for the treatment of psoriasis 6 and under investigation for atopic dermatitis.…”

Trichinella pseudospiralis-secreted 53 kDa protein ameliorates imiquimod-induced psoriasis by inhibiting the IL-23/IL-17 axis in mice

“…In skin psoriasis, Th17-cell-produced IL-17A and IL-17F mainly act on keratinocytes to induce the production of various inflammatory mediators and facilitate the abnormal proliferation of keratinocytes [ 48 ]. When skin tissue receives stimulations, such as trauma, injury, infection, and medication, the stressed or damaged cells in prepsoriatic skins release autoantigens such as nucleic acids, cationic antimicrobial peptides/proteins (AMPs), ADAMTSL-5, and PLA2G4D, which activate DCs and then through IL-23 to activate Th17 cells [ 38 ]. DCs also produce the cytokines IL-6, IL-1β and TNF-α to further enhance Th17-cell differentiation from CD4 + cells, which produce high levels of IL-17A, IL-17F, IL-22 and TNF-α.…”

“…These cytokines in turn activate resident keratinocytes and infiltrating T cells, including IL-17-producing CD4 + T cells (Th17) which produce IL-17A, IL-17F, and other cytokines. Th17-produced cytokines further stimulate keratinocytes, fibroblasts, and innate immune cells to produce a variety of cytokines, chemokines, and AMPs, which promote the expansion of Th17 cells and amplify local inflammatory responses [ 38 ]. Thus, the crosstalk between keratinocytes, innate cells and Th17 cells drives cutaneous inflammation, keratinocyte proliferation and differentiation, and epidermal hyperplasia.…”

Current developments and perspectives in psoriasis

“…In addition to the focus on immunologic (dys)regulation, the pathogenetic significance of other tissue and cell types is also experiencing a scientific renaissance. Recent studies on the "inflammatory memory" of epidermal keratinocytes through epigenetic changes and long-term activation of relevant transcription factors, [82][83][84] or the inflammatory activity of neuronal factors, [85][86][87] warrant particular mention in this context. We believe that research in these areas will also be necessary to further understand the complexity of psoriasis.…”

“…"Immunological memory" has been known for some time in psoriatic skin lesions. 93 But more recently, clinical and experimental evidence is accumulating that suggests a central role of both immunological regulation, for example the central role of so-called tissue resident memory cells, 80,81,93,94 and epithelial "memory functions", [82][83][84] in the initiation, course, and expression of psoriasis. Therefore, we think that especially in connection with the fundamental influence of the disease process (disease modification) the scientific research of such and additional mechanisms will increase.…”