Expression of interleukin (IL)-1 family members upon stimulation with IL-17 differs in keratinocytes derived from patients with psoriasis and healthy donors

Abstract

As keratinocytes were derived from epidermal stem cells of the hair follicles and were obtained from nonlesional sites, differences found are likely to present an intrinsic feature of psoriasis epithelium. Our data support the significance of IL-1 family members as therapeutic targets in psoriasis conditions.

Psoriasiform dermatitis is driven by IL-36–mediated DC-keratinocyte crosstalk

“…IL-36 expression in keratinocytes was enhanced by IL-1α, TNF-α, and IL-17 and downregulated by neutralizing IL-22 (29). IL-17 induced IL-36 agonists more potently in human psoriasis-derived keratinocytes than in healthy keratinocytes, while Il36rn expression remained unaffected (35). Furthermore, IL-36 was able to induce its own expression as well as expression of various proinflammatory cytokines and augmented IL-17-mediated production of antibacterial peptides (29,36).…”

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia

“…There is strong evidence that secondary to immune pathogenetic mechanisms, epidermal factors contribute to the psoriasis disease phenotype through the release of cytokines and chemokines (7,21,(62)(63)(64)(65). While a primary role for the epidermis has been clearly shown in atopic dermatitis (66), a primary role for the epidermis remains open to debate in the psoriasis field.…”

“…IL-17 and IL-22 cytokines produced by Th17/Th22 cells stimulate proliferation and inhibit differentiation of epidermal keratinocytes, thus accounting for the marked epidermal hyperplasia characteristic of psoriasis. Secondarily, the epidermis itself produces a range of cytokines and chemokines that help maintain the disease (3)(4)(5)(6)(7)(8)(9)(10)(11). While copy number polymorphisms in the β-defensins and deletions of the LCE3C/B locus have been associated with psoriasis (12), a primary role for epidermal defects in the pathogenesis of psoriasis is controversial.…”

The Role of Cytokines of Interleukin 36 Family in Immunopathogenesis of Psoriasis

“…Было показано, что бло-кирование передачи сигнала на уровне IL-36R приводило к уменьшению в коже количества нейтрофильных гранулоцитов и макрофагов, значительному снижению экспрессии IL-17A γβ-Т-клетками и разрешению псориатических высыпаний [44]. Цитокины IL-17А, IFNγ, TNFα, IL-22 стимулируют продукцию кератиноцитами агонистов IL-36α, IL-36β, IL-36γ [6,14,23,33]. Представители семейства IL-36, в свою очередь, могут индуцировать секрецию кератиноцитами TNFα, IL-6 и антимикробных пептидов.…”