Interleukin‐25 is involved in cutaneous T‐cell lymphoma progression by establishing a T helper 2‐dominant microenvironment.

Summary: Background: Interleukin (IL)‐25 is a member of the IL‐17 family, which can promote and augment T‐helper (Th) type 2 responses. The expression of IL‐25 and its cognate receptor, IL‐25 receptor (IL‐25R), is upregulated and correlated with disease activity in Th2‐associated diseases. Objectives: To examine the expression and function of IL‐25 in cutaneous T‐cell lymphoma (CTCL). Methods: Expression and location of IL‐25 in lesional skin was investigated with immunohistochemistry. The effect of various cytokines on IL‐25 production from normal human epidermal keratinocytes was assessed by quantitative reverse‐transcription real‐time polymerase chain reaction. Serum IL‐25 levels were measured by enzyme‐linked immunosorbent assay. The direct effect of IL‐25 on tumour cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in patients with Sézary syndrome. Results: IL‐25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL‐4 and IL‐13, and periostin induced IL‐25 expression by normal human epidermal keratinocytes. Serum IL‐25 levels were increased in patients with advanced CTCL and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL‐25R and its expression was augmented by stimulation with IL‐25. IL‐25 enhanced IL‐13 production from MyLa cells via phosphorylation of signal transducer and activator of transcription 6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL‐25R and showed increase of IL‐13 production by IL‐25. Conclusions: Th2 cytokines highly expressed in CTCL lesional skin induce IL‐25 production by epidermal keratinocytes, which may, in turn, lead to formation of a Th2‐dominant microenvironment through the direct induction of IL‐13 by tumour cells. [ABSTRACT FROM AUTHOR]