Psoriasis, stem cells, and obesity: metabolic exploration for therapeutics

Abstract

Psoriasis is a chronic inflammatory cutaneous disease with a complex pathogenesis that remains incompletely understood. New data suggest that psoriasis severity may be more accurately assessed by examining inflammation, oxidative stress, and hormones, although further research is needed to substantiate the clinical value of these biomarkers. The multifactorial causes of psoriasis encompass metabolic deregulations, such as lipid alterations that favor inflammation, exacerbate immune cell activity, and worsen the disease symptomatology. The pathophysiological link between psoriasis and obesity may be revealed through a crosstalk between adipocytes and the immune system, mediated by diverse soluble mediators, including adipokines. In this autoimmune disease, dermal mesenchymal stem cells (MSCs) are potential cellular players that connect autoimmune mechanisms, inflammation, and dysregulation of lipid metabolism. Networks of soluble factors, immune and non-immune cells, and MSCs mediate the inflammatory state in psoriasis. In many recent studies, the relapse has been associated with the potential role of MSCs in this process, endorsing MSCs as a new therapeutic reservoir in psoriasis. Thus, in our review, we aimed to evaluate the potential connection between autoimmunity, inflammation, and dermal mesenchymal stem cells, along with dysregulation of lipid metabolism, to elucidate the identity of psoriasis and identify potential new diagnostic and/or therapeutic targets.

Keywords: immune cells; lipids; obesity; psoriasis; stem cells; therapy.

Figure 1

MSCs' involvement in Pso pathology and therapy. Pso-MSCs can sustain the pathology by inducing hyperplasia of keratinocytes, angiogenesis, and the activation of immune cells, including T lymphocytes, dendritic cells, monocytes, neutrophils, basophils, and eosinophils. Normal MSCs, when infused in Pso patients, can restore symptomatology by lowering the psoriasis area and severity index (PASI score), increasing Tregs and CD4+ memory T cells, and decreasing Th17 and serum IL-17 levels.

Figure 2

The interrelation of the main adipokines with pro-inflammatory cytokines and their effect upon inflammation in Pso

Figure 3

Leptin’s interactions as a key regulator of energy balance and body weight control. Once released into the circulation, leptin will bind to its receptor (LEPR), activating major signalling pathways (JAK2/STAT3 and MAPK cascades). It can bind to several important molecules such as neuropeptide (NP)Y, involved in the control of feeding and the secretion of gonadotropin-releasing hormone. It influences appetite-regulating hormones (ghrelin-obestatin preproprotein GHRL) and adiponectin (ADIPOQ), which are involved in the control of fat metabolism and insulin sensitivity. Additionally, it affects corticotropin-like intermediary peptide (POMC), which stimulates the adrenal glands to release cortisol, and prolactin (PRL), which acts primarily on the mammary gland by promoting lactation. Leptin (LEP) activates insulin A chain (INS) that decreases blood glucose concentration, increases cell permeability to monosaccharides, amino acids, and fatty acids, accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. It also influences glicentin-related polypeptide (GCG), a key mediator of glucose metabolism and homeostasis; agouti-related protein (AGRP), which regulates weight homeostasis; and ciliary neurotrophic factor (CNTF), a survival and regeneration factor for various neuronal cell types. (Network developed using STRING, version 12.0).