Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides

Interleukin (IL)-21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8(+) T cells. In this study, we investigated the role of IL-21 in mycosis fungoides (MF). IL-21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL-21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL-21 in MF lesional skin significantly correlated with those of T-helper type-1 cytokines/chemokines such as CXCL10, CXCL11 and γ-interferon. Immunohistochemistry showed that IL-21 was expressed by keratinocytes in patch and plaque MF. Furthermore, serum IL-21 levels in patients with tumor MF were significantly lower than those of healthy controls and plaque MF. Thus, IL-21 expression was significantly downregulated in skin and blood of patients with tumor MF, which may contribute to progression of MF. Our study suggests that recombinant IL-21 would be a promising therapy for MF.