Skin immunity and its dysregulation in psoriasis

Abstract

The skin is a peripheral lymphoid organ, being the first immunological defense against infections as the initial interface between the organism and the external background. The maintenance of the skin immune homeostasis depends on a finely equilibrium of well-regulated relations between different cells and exogenous pathogens. Inflammatory skin diseases are directly linked to the dysregulation of this equilibrium. The present review discusses the role of the immune system, of T cells, in the etiopathogenesis of psoriasis, illustrating a potential rationale for innovative therapeutic intervention.

Keywords: Psoriasis; biologic therapies; cytokines; immunity; lymphocytes.

Figure 1.

Skin cells. Skin resident cells in the steady state can be divided in innate immune cells: Langerhans cells, dermal dendritic cells, macrophages, other innate cells (mast cell), and adaptative immune cells: memory T cells. Non-immune cells are keratinocytes, fibroblasts and endothelial cells which also participate in immune responses by sensing tissue damage and producing inflammatory cytokines. On activation of the skin-resident immune system, additional immune cells are recruited to help contain and fight infection and/or to remove cellular debris to aid in the healing process (recruited immune cells). These include additional innate cells like neutrophils and eosinophils, as well as adaptive populations like naive or central memory T cells and B cells. T cell activation and differentiation in psoriasis. The figure shows the differentiation of Th lymphocytes in Th 17 producing IL-17, Th22 producing IL-22, Th9 producing IL-9A. Other cytokines implicate in developing psoriasis, acting on skin keratinocytes are IL-23, IL-12, IL-6, TNFalfa and IFN-gamma.

Figure 2.

Structure of the Tumor Necrosis Factor. Mouse Tumor Necrosis Factor in a trimer conformation. The original PDB file is coded as 2TNF. The Color Legend shows he hydrophilic (red)/hydrophobic (green) surface residues for the left panel; while the secondary structure is shown in the central and left panel.

Figure 3.

Structure of the major immunological proteins. (a) Interferons gamma as a single chain, bound to its receptor. The original PDB file is coded as 2TNF 1FYH. (b) Interleukin-23 in a soluble form unbound. The original PDB file is coded as 5MXA. (c) mouse IL-23. The original PDB file is coded as 2L3Y.