Increased Interleukin-19 Expression in Cutaneous T-cell Lymphoma and Atopic Dermatitis

Abstract

Interleukin-19 (IL-19), a pro-inflammatory cytokine known to stimulate the production of T helper type 2 (Th2) cytokines, is induced by IL-17A and highly expressed in the lesional skin of psoriasis and atopic dermatitis (AD). This aim of this study was to investigate whether IL-19 is involved in cutaneous T-cell lym-phoma (CTCL) and AD. IL-19 levels were significantly higher in the sera of patients with AD and those with advanced-stage CTCL than in normal controls, correlating significantly with clinical disease markers. IL-19 mRNA levels in lesional skin of both diseases were significantly elevated. Immunohistochemical staining revealed that IL-19 was expressed in the epidermis of AD skin and CTCL skin. In vitro, IL-17A and IL-4 increased IL-19 mRNA expression in human keratinocytes. Thus, IL-19 was increased in the sera and skin of AD and CTCL. These results suggest that IL-19 is important for bridging Th17 to Th2 in these diseases.

Early immunologic changes during the onset of atopic dermatitis

“…50,51 Overall, this merged Th2/Th17 profile in early pediatric AD is also reflected by a strong up-regulation of IL-19, which is a proinflammatory cytokine typically induced by IL-17, and that can further stimulate production of Th2-associated cytokines, thus bridging Th17 to Th2 immune axes. 52,53 A potential functional role of Th17 activation in early-onset pediatric AD is suggested by the fact that IL-26, a Th17-associated cytokine, showed a strong positive correlation with transepidermal water loss (TEWL) and thus skin barrier impairment. 50 Despite the fact that the pediatric skin samples were fully developed, strongly acanthotic lesions, Th1/IFN-gedependent inflammation (CXCL10, IL12RB2, STAT1, IFNGR1, CXCL9), which is typically seen in chronic lesions in adult AD, was virtually absent in Figure 1.…”

Increased IL-26 Expression Promotes T Helper Type 17- and T Helper Type 2-Associated Cytokine Production by Keratinocytes in Atopic Dermatitis

“…In addition, IL-17A deficiency attenuates AD-like dermatitis and production of IL-4 and immunoglobulin E in a repeated hapten applicationinduced AD model (Nakajima et al, 2014). IL-17A can strongly induce expression of IL-19 by keratinocytes, which in turn augments Th2 cytokine expression in T cells (Liao et al, 2004;Oka et al, 2017;Witte et al, 2014), suggesting that IL-19 possibly bridges between Th2 and Th17 axes. Actually IL-19 is overexpressed in patients with AD, and serum IL-19 levels are correlated with Eczema Area and Severity Index, serum levels of chemokine (C-C motif) ligand 17 (CCL17), and the number of eosinophils (Oka et al, 2017).…”

“…IL-17A can strongly induce expression of IL-19 by keratinocytes, which in turn augments Th2 cytokine expression in T cells (Liao et al, 2004;Oka et al, 2017;Witte et al, 2014), suggesting that IL-19 possibly bridges between Th2 and Th17 axes. Actually IL-19 is overexpressed in patients with AD, and serum IL-19 levels are correlated with Eczema Area and Severity Index, serum levels of chemokine (C-C motif) ligand 17 (CCL17), and the number of eosinophils (Oka et al, 2017). These studies indicate that Th17 cells play an important role in the development of AD and that Th17 responses are also involved in the regulation of Th2 responses.…”

New Cytokines in the Pathogenesis of Atopic Dermatitis—New Therapeutic Targets

“…Interleukin-19 (IL-19) is another pro-inflammatory cytokine that probably stimulates the production of Type 2 T-helper cells (Th2) [ 86 ]. Its gene is on chromosome 1q32.…”

“…Under the influence of IL-17A, IL-19 is strongly expressed in AD lesional skin. This suggests that IL-19 may be important for linking Th17 with Th2 in AD [ 86 ]. Thus, IL-19 seems to be interesting in the search for new drugs that would provide better disease control in patients with AD.…”