Psoriasis: Targets and Therapy (May 2022)
Updated Perspectives on Keratinocytes and Psoriasis: Keratinocytes are More Than Innocent Bystanders
Abstract
Laura I Ortiz-Lopez,1,2 Vivek Choudhary,1,3 Wendy B Bollag1,3– 5 1Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA; 2Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA; 3Charlie Norwood VA Medical Center, Augusta, GA, 30904, USA; 4Department of Dermatology, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA; 5Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USACorrespondence: Wendy B Bollag, Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, USA, Tel +1 706 721-0698, Fax +1 706 721-7299, Email [email protected]: Psoriasis is a complex disease triggered by genetic, immunologic, and environmental stimuli. Many genes have been linked to psoriasis, like the psoriasis susceptibility genes, some of which are critical in keratinocyte biology and epidermal barrier function. Still, the exact pathogenesis of psoriasis is unknown. In the disease, the balance between the proliferative and differentiative processes of keratinocytes becomes altered. Multiple studies have highlighted the role of dysregulated immune cells in provoking the inflammatory responses seen in psoriasis. In addition to immune cells, accumulating evidence shows that keratinocytes are involved in psoriasis pathogenesis, as discussed in this review. Although certain immune cell-derived factors stimulate keratinocyte hyperproliferation, activated keratinocytes can also produce anti-microbial peptides, cytokines, and chemokines that can promote their proliferation, as well as recruit immune cells to help initiate and reinforce inflammatory feedback loops. Psoriatic keratinocytes also show intrinsic differences from normal keratinocytes even after removal from the in vivo inflammatory environment; thus, psoriatic keratinocytes have been found to exhibit abnormal calcium metabolism and possible epigenetic changes that contribute to psoriasis. The Koebner phenomenon, in which injury promotes the development of psoriatic lesions, also provides evidence for keratinocytes’ contributions to disease pathogenesis. Furthermore, transgenic mouse studies have confirmed the importance of keratinocytes in the etiology of psoriasis. Finally, in addition to immune cells and keratinocytes, data in the literature support roles for other cell types, tissues, and systems in psoriasis development. These other contributors are all potential targets for therapies, suggesting the importance of a holistic approach when treating psoriasis.Keywords: anti-microbial peptides, inflammation, innate immunity, Koebner phenomenon, skin
