Keratinocyte: A trigger or an executor of psoriasis?

Abstract

Psoriasis is a common chronic inflammatory skin disease characterized by abnormal proliferation/differentiation of keratinocytes and excessive immune cell infiltration in the dermis and epidermis. Over the past 2 decades, immune cells have been considered as the main driver of psoriasis because the neutralizing antibodies targeting the IL-23/IL-17 axis that regulates cross-talk between dendritic cells and T cells achieve tremendous success in the treatment of psoriasis. However, whether keratinocyte would be a driver of psoriasis or just an executor in response to immune cells is still under debate. In this review, we focus on the recent advances in the identification of keratinocyte as a trigger of psoriasis, summarize on the role of keratinocytes in self-perpetuating loop to maintain inflammation in psoriasis, and then discuss the possible roles of keratinocytes in the relapse of psoriasis.

miRNAs Flowing Up and Down: The Concerto of Psoriasis

“…Hallmarks of psoriasis include keratinocyte hyperproliferation and abnormal differentiation, accompanied by the aberrant production of inflammatory cytokines and chemokines from keratinocytes (5). By reviewing recent literature, we find that among the differentially expressed miRNAs in psoriasis, several miRNAs form a complementary regulatory network to impair the balance between proliferation and differentiation of keratinocytes.…”

“…Herein, interleukins (ILs) (IL-1, IL-17, IL-22, IL-23, etc. ), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β) are key players for cell-cell crosstalks (3)(4)(5). As for the non-protein-coding regulatory elements, altered miRNA expression profiles were uncovered in psoriatic skin, blood, and hair samples (6,7), which profoundly influences our knowledge of the driving force and regulatory counterpart in psoriasis.…”

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

“…However, T cells were later discovered to play a role in the pathogenesis. Therefore, it is now believed that the crosstalk between keratinocytes and immune cells, particularly T cells and dendritic cells, plays critical roles in the pathogenesis of psoriasis [ 45 ]. Anne Bowcock, a geneticist at Washington University in St. Louis, gave the first indication that keratinocytes play a major role in the development of psoriasis.…”

“…Rag2-deficient JunB/c-Jun double-mutant mice showed epidermal thickening, altered keratinocyte differentiation, vascular dilatation and slight epidermal abscesses [ 56 ]. The debate over whether abnormalities in the keratinocytes or of the immune system are responsible for triggering the disease is still emerging, suggesting a dynamic contribution of keratinocytes to the pathogenesis [ 45 , 46 , 57 , 58 ].…”

IL‐23 modulates histamine‐evoked itch and responses of pruriceptors in mice

“…[ 4 ] One of the areas in which itch plays a large role is inflammatory skin diseases, such as atopic dermatitis and psoriasis. [ 3,5 ] These inflammatory skin disorders are often associated with severe chronic itch, which can lead to an extreme decrease in quality of life. [ 6‐8 ] Recent findings suggest that neuro‐immune interactions are associated with itch initiation and augmentation in inflammatory skin diseases.…”