Progress in understanding the immunopathogenesis of psoriasis

Abstract

This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed.

Figure 1

Potential of HLA-Cw6 to regulate adaptive as well as innate immune responses. HLA-Cw6 expressed on antigen presenting cells (APCs) such as dendritic cells can trigger adaptive immune responses via presentation of processed antigen to the TCR of CD8+ T cells. In addition, innate immune response can be elicited by interaction of HLA-Cw6 with its natural Killer immunoglobulin-like receptors expressed on NK and NKT cells.

Figure 2

Role of CD4 T cell subtypes in psoriasis. Pro-inflammatory cytokines produced from Th1 and Th17 dominate the cytokine profile in psoriasis. They mediate keratinocyte hyperproliferation and trigger a ‘vicious cycle’ of inflammation. IL-23 released by psoriatic keratinocytes and sentinel cells such as dendritic cells and macrophages, is critical for maintenance of Th17 function. Low levels of anti-inflammatory cytokines released by Th2 and Treg cells potentially counteract but cannot balance the effects of Th1/Th17 cytokines. Green arrows denote stimulatory actions, red blocking lines denote inhibitory actions.

Figure 3

Immune cell types and interactions implicated in psoriasis. Green dot denotes Th1 cytokines including IFNg and TNFa. Purple dot denotes cytokines produced by Th17 including IL17A, IL17F and IL22. Red dot denotes other inflammatory mediators such as IL-2 and IL-6. Low levels of anti-inflammatory cytokines released by Th2 and Treg cells potentially counteract but cannot balance the effects of Th1/Th17 cytokines. Th1 and Th2 cells have a mutually inhibitory effect as denoted by the red line. Treg inhibits Th1 actions as denoted by the red arrow.