Pathogenesis of psoriasis in the "omic" era. Part I. Epidemiology, clinical manifestation, immunological and neuroendocrine disturbances

Abstract

Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world's population. According to current knowledge, psoriasis is a complex disease that involves various genes and environmental factors, such as stress, injuries, infections and certain medications. The chronic inflammation of psoriasis lesions develops upon epidermal infiltration, activation, and expansion of type 1 and type 17 Th cells. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the target cells and antigens that drive pathogenic T cell responses in psoriatic lesions are still unproven and the autoimmune basis of psoriasis still remains hypothetical. However, since the identification of the Th17 cell subset, the IL-23/Th17 immune axis has been considered a key driver of psoriatic inflammation, which has led to the development of biologic agents that target crucial elements of this pathway. Here we present the current understanding of various aspects in psoriasis pathogenesis.

Keywords: autoimmunity; interleukins; neoangiogenesis; neurogenic inflammation; psoriasis.

Figure 1

Modulated expression of the HPA axis elements underlies the development or aggravation of psoriasis. The immune-stimulatory activities of the upper arm of the cutaneous HPA axis are expected to be amplified by bidirectional communication between CRH/urocortin signaling and locally produced cytokines, unless attenuated by immune-inhibitory POMC peptides including ACTH, α-MSH and β-endorphin (whose local production is stimulated by both CRH related peptides and/or selected cytokines) and/or terminated by glucocorticoids, which possibly serves as a counter-regulatory mechanism to avoid excessive inflammation CYT – proinflammatory cytokines, CRH – corticotropin-releasing hormone, UCN – urocortins 1-3, CRHR1/CRHR2 – CRH receptor type 1 and 2, POMC – proopiomelanocortin, β-END – β-endorphin, MSH – melanocyte stimulating hormone, ACTH – adrenocorticotropic hormone, CHOL – cholesterol, G-OH – cortisol and corticosterone, G=O – cortisone and 11-dehydrocorticosterone, GR – glucocorticoid receptor (NR3C1).