Abstract
Autoinflammatory and autoimmune diseases are characterized by an oversensitive immune system with loss of the physiological endogenous regulation, involving multifactorial self-reactive pathological mechanisms of mono- or polygenic nature. Failure in regulatory mechanisms triggers a complex network of dynamic relationships between innate and adaptive immunity, leading to coexistent autoinflammatory and autoimmune processes. Sustained exposure to a trigger or a genetic alteration at the level of the receptors of the natural immune system may lead to abnormal activation of the innate immune system, adaptive system activation, loss of self-tolerance, and systemic inflammation. The IL-1 family members critically activate and regulate innate and adaptive immune responses' diversity and plasticity in autoimmune and/or autoinflammatory conditions. The IL-23/IL-17 axis is key in the communication between innate immunity (IL-23-producing myeloid cells) and adaptive immunity (Th17- and IL-17-expressing CD8+ T cells). In psoriasis, these cytokines are decisive to the different clinical presentations, whether as plaque psoriasis (psoriasis vulgaris), generalized pustular psoriasis (pustular psoriasis), or mixed forms. These forms reflect a gradient between autoimmune pathophysiology with predominant adaptive immune response and autoinflammatory pathophysiology with predominant innate immune response.
Highlights
Autoinflammatory and autoimmune diseases are characterized by immune system hyperactivity, typically featuring an against-self pathological process
We examine current knowledge on the inflammatory role of the IL-1 cytokine family, their association with the inflammasome in autoinflammatory and autoimmune disorder regulation, and the underlying implication of innate and adaptive immunity in diseases with a mixed pathogenic pattern, with particular focus on psoriasis [4]
The pathophysiological role of IL-1β is well established in autoinflammatory diseases, and IL-1β and IL-18 are critically associated with severity in various autoimmune and chronic inflammatory pathologies [7]
Summary
Autoinflammatory and autoimmune diseases are characterized by immune system hyperactivity, typically featuring an against-self pathological process. An adaptive immune dysregulation—against self—is found in autoimmune diseases Both combined are present in mixed autoinflammatory-autoimmune pattern diseases (Figure 1). Mutations in genes related to the inflammasome have been associated with autoinflammation This multiprotein complex has been associated with organ-specific autoimmunity since a wide spectrum of endogenous danger signals can activate inflammasome products, including IL-1β, triggering adaptive immunity pathways [3]. Genetic predisposition involves many loci encoding key immune pathway molecules These genes are under epigenetic control, influenced by several environmental factors in susceptible individuals. We examine current knowledge on the inflammatory role of the IL-1 cytokine family, their association with the inflammasome in autoinflammatory and autoimmune disorder regulation, and the underlying implication of innate and adaptive immunity in diseases with a mixed pathogenic pattern, with particular focus on psoriasis [4]
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