Interleukin-1 Links Autoimmune and Autoinflammatory Pathophysiology in Mixed-Pattern Psoriasis

Figure 3

Schematic representation of inflammasome signaling mechanisms in mixed-pattern inflammatory diseases. Inflammatory agents and pathogens trigger the canonical inflammasome pathway. PAMPs and DAMPs are detected by specific innate immune sensors, leading to oligomerization and inflammasome assembly. The therapeutic targets in autoinflammatory diseases are as follows: signal 1 inflammasome activation: surface pattern recognition receptors like Toll-like receptors (TLR) and pathogen-associated molecular patterns stimulate the production of molecules like NF-κB and activate inflammasome assembly through downstream immunologic processes; signal 2 inflammasome activation: crystals in gout, heat-shock proteins, and damaged tissue as in burns, another pathogen- and damage-associated molecular pattern, activate inflammasome assembly through reactive oxygen species (ROS) production and downstream immunologic processes. Certain mediators influence the spectrum of psoriasis, shifting to innate or adaptive immune processes. The interplay between IL-17- and IL-36-driven inflammation seems involved in innate-adaptive immune balance. Inflammasome-induced hyperactive dendritic cells (DC) trigger enhanced T cell responses, preserving antigen and autoantigen presentation and contextualizing T helper cell responses through IL-1β, IL-18, and IL-23 secretion. These cytokines trigger Th1/Th17 responses. IL-18 amplifies IFN-γ production by Th1 cells and reinforces Th1 differentiation, while IL-1β promotes Th17 polarization and IL-17 secretion, causing a mixed autoinflammatory-autoimmune pathology. The image shows the potential sites for antibody-based therapeutic intervention (ABTI). ASC: apoptosis-associated speck protein; ER: endoplasmic reticulum; IFNAR: interferon-associated receptor; IFN: interferon; IL-1: interleukin-1; IL-1 R: IL-1 receptor; IL-1Ra: IL-1 receptor antagonist; IL-6: interleukin 6; IL-6R: IL-6 receptor; IL-18: interleukin-18; JAK: Janus kinase; NLRP3: NOD-like receptor P3; ROS: reactive oxygen species; TLR: Toll-like receptor; TNF: tumor necrosis factor; TNF-R: TNF receptor; ASC: apoptosis-associated speck-like protein containing a CARD; CARD: caspase recruitment domain; DAMP: damage-associated molecular pattern; LPS: lipopolysaccharide; NLR: NOD-like receptor; NOD: nucleotide-binding oligomerization domain; PAMP: pathogen-associated molecular pattern; PYD: Pyrin domain; MMC: multimolecular complex; HMGB1: high-mobility group box 1; TCR: T cell receptor.