Psoriasis mechanism and therapies (Homo sapiens)

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Psoriasis can be triggered by environmental stressors and physical trauma, particularly in individuals with genetic predispositions such as PSORS1. These triggers promote the release of chemokines CCL20, CXCL8, and CXCL1, which in turn recruit CCR6⁺IL-17⁺ lymphocytes, neutrophils, and IL-23⁺CD14⁺ dendritic cells (DCs), respectively. IL-17-producing cells -- including Th17, Tc17, and ILC3 -- release IL-17A and IL-17F, which activate the IL-17RA/IL-17RC receptor complex on keratinocytes, amplifying the inflammatory cascade. Additionally, IL-22 produced by ILC3 cells contributes to keratinocyte hyperproliferation. Dendritic cells further release pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-23. IL-23 promotes the expansion and activity of IL-17-producing cells via the JAK2/TYK2-STAT3 signaling pathway.

Targeted therapies include ustekinumab (brand name Stelara), which blocks the p40 subunit shared by IL-12 and IL-23, and guselkumab (Tremfya) and risankizumab (Skyrizi), which inhibit the IL-23-specific p19 subunit. IL-17A is targeted by secukinumab (Cosentyx) and ixekizumab (Taltz), while bimekizumab (Bimzelx) neutralizes both IL-17A and IL-17F. Brodalumab (Siliq, Kyntheum) inhibits IL-17RA, disrupting downstream signaling. For JAK pathway inhibition, deucravacitinib (Sotyktu) selectively targets TYK2, and brepocitinib inhibits both TYK2 and JAK1.

Inspired by Figure 1 in [Song et al. (2022)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8901701/).