A role for T cell-derived interleukin 22 in psoriatic skin inflammation

Abstract

Interleukin (IL)-22 is a T cell-derived cytokine that has been reported recently to induce cutaneous inflammation in an experimental murine model of psoriasis, and to induce in vitro an inflammatory-like phenotype. In the present study, we assessed the presence of IL-22 and the IL-22 receptor 1 (IL-22R1) in skin lesions, skin-derived T cells, as well as IL-22 levels in sera from patients with psoriasis. IL-22R1 and IL-10R2 transcripts are expressed at a similar level in psoriatic and healthy skin. In contrast, IL-22 mRNA expression was up-regulated in psoriatic skin lesions compared to normal skin, whereas IL-22 mRNA levels in peripheral blood mononuclear cells from psoriatic patients and normal subjects were similar. Circulating IL-22 levels were significantly higher in psoriatic patients than in normal subjects. T cells isolated from psoriatic skin produced higher levels of IL-22 in comparison to peripheral T cells isolated from the same patients. IL-10 was expressed at similar levels in skin biopsies and peripheral blood mononuclear cells of psoriatic patients and normal subjects. Finally, we show here that supernatants of lesional psoriatic skin-infiltrating T cells induce an inflammatory response by normal human epidermal keratinocytes, resembling that observed in psoriatic lesions. Taken together, the results reported in this study indicate that IL-22 is a cytokine produced by skin-infiltrating lymphocytes that is potentially involved in initiation and/or maintenance of the pathogenesis of psoriasis.

Mechanisms of Rapid Induction of Interleukin-22 in Activated T Cells and Its Modulation by Cyclosporin A

“…As already alluded to, IL-22 has been identified as a key pathogenic molecule in experimental psoriasis (22). In fact, IL-22 is up-regulated in psoriasis patients' sera (62) and highly expressed in lesional skin tissue (63). Biological functions possibly underlying disease promotion by IL-22 include modulation of keratinocyte differentiation and induction of proinflammatory cytokines, chemokines, and matrix metalloproteinases, among others IL-20, CXCL5, and matrix metalloproteinases-1/3 (18,61,62,64,65).…”

Multiparameter grouping delineates heterogeneous populations of human IL‐17 and/or IL‐22 T‐cell producers that share antigen specificities with other T‐cell subsets

“…Instead, IL-22 acts mainly on epithelial cells of the digestive and respiratory tracts, as well as on epidermal keratinocytes where it is involved in the induction of b-defensins and epithelium homeostasis [20,21]. High IL-22 expression in skin lesions and serum levels of patients with active psoriasis suggests deleterious effects of this cytokine on tissue inflammation [22,23]. Indeed, recent biologic therapies for psoriatic patients include anti-IL-23 treatment, a cytokine directly involved in the expansion of IL-17-and IL-22-secreting CD4 1 T cells [24,25].…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…These small cationic proteins kill bacteria and fungi, and are normally expressed in skin and mucosal epithelia, acting as an innate immunity barrier against microbial infections [38,39]. Besides inducing the expression of antimicrobial genes, IL-22 also regulates cellular differentiation and motility of keratinocytes, thereby exerting a spectrum of activities that are beneficial during wound healing and infectious processes, but that contribute to skin lesions of patients with psoriasis disease [16,35,37,[40][41][42].…”