New insights of T cells in the pathogenesis of psoriasis

Abstract

Psoriasis is one of the most common immune-mediated chronic, inflammatory skin diseases characterized by hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages and neutrophils. Although the pathogenesis of psoriasis is not fully understood, there is ample evidence suggesting that the dysregulation of immune cells in the skin, particularly T cells, plays a critical role in psoriasis development. In this review, we mainly focus on the pathogenic T cells and discuss how these T cells are activated and involved in the disease pathogenesis. Newly identified 'professional' IL-17-producing dermal γδ T cells and their potential role in psoriasis will also be included. Finally, we will briefly summarize the recent progress on the T cell and its related cytokine-targeted therapy for psoriasis treatment.

Figure 1

Dysregulated immune responses in psoriasis. Pathogen components or DAMPs activate the DCs and macrophages to produce IL-23, IL-1β and other pro-inflammatory cytokines including IL-6 and TNF-α. These cytokines induce dermal γδ T cells activation and expansion to secrete IL-17, IL-22 and TNF-α, which in turn further promote the conventional CD4⁺ T cell-mediated (Th1, Th17 and Th22) and CD8⁺ T cell-mediated (Tc1) acquired immune responses. In addition, skin infiltrating inflammatory cells, such as mast cells, neutrophils, NK cells and NK T cells, also contribute to the disease development via producing cytokines (IL-17), antimicrobial peptides and cytotoxic granules. Additionally, the dysfunctional Tregs lose their suppressive activity and some of them are able to convert to Th17 effector cells, further enhancing the inflammatory reaction in the local skin. The pro-inflamamtory cytokines and chemokines act on keratinocytes and induce keratinocyte hyperproliferation. The activated keratinocytes also produce some chemokines, such as CCL20 and CXCL1, 3, 8–11, to attract more immune effector cells infiltrating into skin, forming the amplified positive feedback loop, leading to the development of psoriatic lesions. DAMP, damage-associated molecular pattern; DC, dendritic cell; NK, natural killer; Th, T helper; TNF, tumor-necrosis factor; Treg, regulatory T cell.