Current knowledge on psoriasis and autoimmune diseases

Abstract

Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) and T cells. Exclusive cellular "responsibility" for the induction and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Despite the identification of numerous susceptibility loci, no single genetic determinant has been identified as responsible for the induction of psoriasis. Thus, numerous other triggers of disease, such as environmental, microbial and complex cellular interactions must also be considered as participants in the development of this multifactorial disease. Recent advances in therapeutics, especially systemic so-called "biologics" have provided new hope for identifying the critical cellular targets that drive psoriasis pathogenesis. Recent recognition of the numerous co-morbidities and other autoimmune disorders associated with psoriasis, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus suggest common signaling elements and cellular mediators may direct disease pathogenesis. In this review, we discuss common cellular pathways and participants that mediate psoriasis and other autoimmune disorders that share these cellular signaling pathways.

Keywords: autoimmunity; immunosuppression; psoriasis.

Figure 1

Key signals in psoriasis development. Notes: Numerous cellular mediators and signaling pathways are activated in psoriatic lesions following diverse triggers. In the background of individuals expressing a favorable genetic predisposition toward a hyperactive immune response (quiescent panel), these mediators drive a proinflammatory response (flare panel). The proinflammatory state progressively overwhelms the immune counter-balancing mechanisms, and skin proliferation becomes uncontrollable by conventional regulatory cells and suppressive mediators (eg, Treg, IL-10, TGFβ; Chronic/recurrent panel). This exacerbated inflammation results in the progressive creation of resident memory self-reactive cells that in-turn contribute to recruiting inflammatory mediators that result in a life-long recurrent chronic inflammatory skin disease. Abbreviations: CD8 CM, CD8 central memory; Treg, regulatory T cell; NK, natural killer; Th, T helper; TipDC, TNF-iNOS-producing DC; NETs, neutrophil extracellular traps.