Mechanobiology of neutrophil inflammasome signaling in psoriasis

While T cells play a prominent role, polymorphonuclear neutrophils (PMN) are also significant players in the pathogenesis of psoriasis. This review details the mechanobiology of PMN in the amplification of skin inflammation, a process often under-scrutinized compared to T cell pathways. PMN surveillance of skin microcirculation involves selectin-mediated rolling that transitions to stable β 2 -integrin–mediated arrest. Upon tissue recruitment, PMN trigger the NLRP3 inflammasome and NETosis, releasing neutrophil extracellular traps, proinflammatory cytokines including IL-1β and IL-18, and damage-associated molecular patterns. These mediators promote keratinocyte proliferation and recruit additional waves of PMN that contribute to a positive feedback loop that sustains skin inflammation and hyperproliferation of keratinocytes. Consequently, assays measuring PMN activation provide a sensitive biomarker for the progression of psoriatic disease. Furthermore, therapeutically targeting upstream mechanosignaling pathways presents a novel therapeutic avenue to move beyond conventional strategies that block downstream cytokines critical for immunocompetence.