Psychological Stress, Mast Cells, and Psoriasis-Is There Any Relationship?

Abstract

Psoriasis vulgaris is a common inflammatory skin disease with still unknown pathogenesis. In recent years, genetic and environmental factors have been mentioned as the main causes. Among environmental factors, many researchers are trying to investigate the role of mental health and its importance in the development of many diseases. In the pathophysiology of psoriasis, the role of the interaction between the nervous, endocrine, and immune systems are often emphasized. So far, no one has clearly indicated where the pathological process begins. One of the hypotheses is that chronic stress influences the formation of hormonal changes (lowering the systemic cortisol level), which favors the processes of autoimmunity. In inflammatory skin conditions, mast cells (MCs) are localized close to blood vessels and peripheral nerves, where they probably play an important role in the response to environmental stimuli and emotional stress. They are usually connected with a fast immune response, not only in allergies but also a protective response to microbial antigens. Among many cells of the immune system, MCs have receptors for the hormones of the hypothalamic-pituitary-adrenal (HPA) axis on their surface. In this review, we will try to take a closer look at the role of MCs in the pathophysiology of psoriasis. This knowledge may give the opportunity to search for therapeutic solutions.

Keywords: autoimmune disease; mast cells; mental health; psoriasis; psychological stress.

Figure 1

Mast cells and their communication with other cells of the immune system via the surface molecules. MCs participate in the innate and adaptive immune system response. The immunophenotype of MCs is not homogenous: it may vary depending on the current activity or location. MCs contact T cells indirectly via dendritic cells or directly via adhesion molecules: ICAM-1-ligand for T cell CD11a; MHC-II molecules (activation of CD4 + T cell) and MHC-I (activation of CD8 + T cell and Treg proliferation); CD80 and CD86 costimulatory molecules-ligands for CD28 T cells; OX40L (CD252) for OX40 (CD143) to Treg (redirection of the Treg immunophenotype into Th17; suppression degranulation MCs). TLRs, which bind numerous bacterial peptides, play a key role in the MCs as innate immune cells. The following combinations activate the degranulation of MCs: TLR-4 receptor binds bacterial lipopolysaccharides; TLR-5 to flagellin (a protein that builds the bacterial flagellum), the CD48-FimH adhesin present in Escherichia coli, and involved in the response to Streptococcus aureus and Mycobacterium tuberculosis. MCs, as inhibitors of the inflammatory process, show activity by secreting IL-10 and TGF-β, which reduce the activity of macrophages and dendritic cells. Tc (cytotoxic T lymphocyte; CD8+), Treg (regulatory T lymphocyte), Th (helper T lymphocyte, CD4 +), MC (mast cell) [33,36].

Figure 2

The influence of psychological stress on the activation of mast cells and the development of neuroinflammation in psoriasis. Vascular endothelial growth factor (VEGF), corticotrophin-releasing hormone (CRH), substance P (SP), pituitary adenylate cyclase-activating polypeptide (PACAP), nerve growth factor (NGF).