The Immunology of Psoriasis-Current Concepts in Pathogenesis

Abstract

Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades of intense research uncovered a pathological network of interactions between immune cells and other types of cells in the pathogenesis of psoriasis. Emerging evidence indicates that dendritic cells, T_H17 cells, and keratinocytes constitute a pathogenic triad in psoriasis. Dendritic cells produce TNF-α and IL-23 to promote T cell differentiation toward T_H17 cells that produce key psoriatic cytokines IL-17, IFN-γ, and IL-22. Their activity results in skin inflammation and activation and hyperproliferation of keratinocytes. In addition, other cells and signaling pathways are implicated in the pathogenesis of psoriasis, including T_H9 cells, T_H22 cells, CD8⁺ cytotoxic cells, neutrophils, γδ T cells, and cytokines and chemokines secreted by them. New insights from high-throughput analysis of lesional skin identified novel signaling pathways and cell populations involved in the pathogenesis. These studies not only expanded our knowledge about the mechanisms of immune response and the pathogenesis of psoriasis but also resulted in a revolution in the clinical management of patients with psoriasis. Thus, understanding the mechanisms of immune response in psoriatic inflammation is crucial for further studies, the development of novel therapeutic strategies, and the clinical management of psoriasis patients. The aim of the review was to comprehensively present the dysregulation of immune response in psoriasis with an emphasis on recent findings. Here, we described the role of immune cells, including T cells, B cells, dendritic cells, neutrophils, monocytes, mast cells, and innate lymphoid cells (ILCs), as well as non-immune cells, including keratinocytes, fibroblasts, endothelial cells, and platelets in the initiation, development, and progression of psoriasis.

Keywords: Immune response; Keratinocyte; Psoriasis; Skin inflammation; TH17 cells.

Fig. 1

Dysregulation of immune response in psoriasis. Psoriasis may be triggered by different factors, including skin injury (Koebner phenomenon), infection, drugs, and autoantigens in predisposed individuals. In the early phase of psoriasis, neutrophils infiltrate the skin and release neutrophils extracellular traps (NETs), exosomes, metalloproteinase 9 (MMP9), and IL-17. Activated keratinocytes (KCs) have increased proliferative capacity and produce a variety of pro-inflammatory factors, including chemokines, antimicrobial peptides (AMPs), and alarmins. Dendritic cells (DCs) are activated by toll-like receptors (TLRs) ligands and AMPs which initiate T cell immune response. DCs activate a variety of T cells, including IL-17-producing T_H17 and Tc17 cells, IL-9-producing T_H9 cells, IFN-γ-producing T_H1 cells, and IL-22-producing T_H22 cells. Moreover, DCs and Langerhans cells (LCs) can present autoantigens stimulating autoreactive T cells. The impaired skin microbiome activates γδ T cells that produce IL-17 and IL-1β. In the late phase of inflammation, psoriatic lesions are characterized by the profound infiltration of immune cells, increased concentrations of multiple cytokines and chemokines, and hyperproliferation of KCs. Moreover, increased angiogenesis and endothelial cells activated by psoriatic cytokines facilitate the infiltration of immune cells into inflamed skin. Created with Biorender.com

Fig. 2

Cytokine network and therapeutic targets in psoriasis. Immune response in psoriasis is associated with the activation of type 1, type 17, and type 22 pathways and innate inflammatory pathways. These signaling pathways induce the expression of different genes involved in the regulation of psoriatic inflammation (orange boxes). Several biological drugs targeting key psoriatic cytokines (indicated in red) or small molecule inhibitors of downstream cytokine signaling were developed and approved by the FDA. PsA, psoriasis arthritis; PP, pustular psoriasis. Created with Biorender.com

Fig. 3

The role of immune cells in psoriasis. The key populations of immune cells and their functions in the regulation of psoriatic inflammation. Created with Biorender.com