The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

Abstract

Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain–skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.

Is There a Relationship Between Psoriasis and Hepatitis C?: a Meta-analysis and Bioinformatics Investigation

“…The results showed that 398 overlapping gene targets were obtained through PPI analysis, such as IL6, TNF, IL10 and other immune-related in ammatory factors. Many previous studies have shown that psoriasis is an immune-related disease based on T lymphocytes, which is mainly manifested in the imbalance of the balance between different cytokines and the imbalance of complex interactions in tissue disease [33]. It is well known that the in ammatory state associated with hepatitis C virus infection not only affects the liver, but also affects the entire complicated body system [34].…”

Is there a relationship between psoriasis and hepatitis C? A meta-analysis and bioinformatics investigation

“…The results showed that 398 overlapping gene targets were obtained through PPI analysis, such as IL6, TNF, IL10 and other immune-related inflammatory factors. Many previous studies have shown that psoriasis is an immune-related disease based on T lymphocytes, which is mainly manifested in the imbalance of the balance between different cytokines and the imbalance of complex interactions in tissue disease [ 33 ]. It is well known that the inflammatory state associated with hepatitis C virus infection not only affects the liver, but also affects the entire complicated body system [ 34 ].…”

Skin-brain axis signaling mediates behavioral changes after skin wounding

“…The ‘skin-brain axis’ communication network has been recognized as a mechanism by which the central nervous system (CNS) response to psychological stress results in an afferent relay and physiological outcome in the skin ( Paus et al., 2006 ; Pavlovic et al., 2008 ; Martins et al., 2020 ; Rodriguez-Vallecillo and Woodbury-Farina, 2014 ; Chapman and Moynihan, 2009 ). Stress, through a CNS-mediated mechanism, has been shown to exacerbate peripheral cutaneous manifestations of atopic dermatitis, psoriasis, and even hair growth ( Martins et al., 2020 ; Alexopoulos and Chrousos, 2016 ; Ayasse et al., 2020 ; Paus, 2016 ; Pondeljak and Lugović-Mihić, 2020 ; Theoharides, 2020 ; Torales et al., 2020 ; Yang and Zheng, 2020 ; Zeiser et al., 2021 ). However, in addition to the skin being a target for stress responses, bi-directional signaling is described wherein the skin itself, through the localized production of neuroimmunomodulators and stress catecholamines, can initiate stress signaling to the brain ( Paus et al., 2006 ; Chen and Lyga, 2014 ).…”