Psoriasis is a chronic, immune-mediated skin disorder [1] characterized by sustained inflammation, uncontrolled keratinocyte proliferation, dysfunctional differentiation, and angiogenesis [1], [2], [3], [4]. Studies estimate that around 125 million people worldwide are affected by this condition [5]. It can occur at any age, with peak onset usually observed during early adulthood. The prevalence is higher in developed countries, which may be attributed to a mix of genetic predisposition, lifestyle factors, and environmental triggers [5], [6]. Not only does psoriasis cause physical discomfort, including itching, pain, and restricted joint movement in severe cases, but it also carries significant psychological and social burdens. Although psoriasis seldom results in immediate fatality, its correlation with multiple comorbidities, including cardiovascular ailments, diabetes, and depression, markedly increases the rates of disability and mortality [7], [8]. Therefore, unraveling the intricacies of psoriasis pathogenesis is crucial for developing targeted therapeutic strategies.

Autophagy, also known as 'self-eating', is a cellular process in which cytoplasmic materials are degraded in the lysosome [9], [10]. Perhaps the most primordial function of this lysosomal degradation pathway is adaptation to nutrient deprivation [9]. It serves the primary purpose of maintaining intracellular stability and enabling cellular adaptation to unfavorable circumstances. There are three types of autophagy that differ in how cargo is delivered to the lysosome: macroautophagy, microautophagy, and chaperone-mediated autophagy. Macroautophagy is the main regulated form of autophagy, which responds to environmental and physiological cues. Microautophagy involves the direct engulfment of cytoplasmic contents by lysosomes, while chaperone-mediated autophagy involves the assistance of chaperones in transporting substrate proteins (and possibly DNA and RNA) across the lysosomal membrane. In this review we specifically focus on the process of macroautophagy in psoriasis [11], [12].

Within the macroautophagy process (Fig. 1), a portion of the cytoplasm becomes encapsulated by a membranous structure termed the isolation membrane or phagophore, ultimately giving rise to the formation of a dual-membrane organelle known as the autophagosome [13]. Subsequent to the fusion of the outer autophagosomal and lysosomal membranes, lysosomal enzymes initiate the degradation of the inner autophagosomal membrane and its contents. Macroautophagy exhibits selectivity and possesses the capacity to specifically degrade impaired mitochondria (referred to as mitochondrial autophagy), ruptured lysosomes (known as lysosome autophagy), and intracellular microorganisms (termed heterologous autophagy) [14], [15]. The macroautophagy process, commonly referred to as autophagy, entails the coordinated action of various protein complexes encoded by a set of evolutionarily conserved genes known as autophagy-related (ATG) genes [16]. Initially discovered in yeast, these 15 core ATG genes (ATG1 through ATG10, ATG12, ATG13, ATG14, ATG16, and ATG18) play a crucial role in both nonselective and selective autophagy, maintaining their conservation throughout evolution. ATG11, also identified as RB1CC1, and ATG101 are considered essential ATG genes in various organisms, excluding yeast [13], [17]. Alongside additional membrane traffic factors, these 15 or 17 ATG genes govern distinct stages of autophagosome formation, encompassing induction, typically triggered by metabolic stresses such as starvation. They contribute to processes like membrane nucleation, elongation on the endoplasmic reticulum, closure, and tethering, as well as fusion with lysosomes [13], [14], [16], [17].

There is strong evidence supporting the involvement of autophagy in viral and bacterial infectious dermatoses, skin cancer, and autoimmune skin diseases [18], [19]. Recent studies have highlighted the importance of autophagy in psoriasis and other inflammatory skin diseases [20]. Dysregulated autophagy has been identified in psoriatic lesions and is believed to play a role in the excessive proliferation of keratinocytes characteristic of psoriasis [20], [21]. Inhibiting autophagy leads to increased production of IL-17A and other inflammatory cytokines that drive psoriasis pathogenesis [22], [23]. Thus, restoring normal autophagy has become a novel therapeutic approach for treating psoriasis [20], [21], [22]. Multiple natural compounds like fisetin [22] and fenofibrate [23] have been found to reduce psoriasis-like inflammation in mice by stimulating autophagy. These treatments alleviate symptoms by simultaneously inhibiting mTOR and IL-17A signaling, two key drivers of psoriasis [22]. Additionally, promoting autophagy may limit keratinocyte proliferation and activation of inflammatory immune cells [20]. In summary, impaired autophagy contributes to the development of psoriasis and other inflammatory skin diseases. Therapies aimed at restoring normal autophagy hold promise for treating these conditions by blocking aberrant immune responses and keratinocyte hyperproliferation.