Defective Epidermal Innate Immunity and Resultant Superficial Dermatophytosis in Adult T-cell Leukemia/Lymphoma

Purpose: Superficial dermatophytosis is quite commonly seen in patients with adult T-cell leukemia/lymphoma (ATLL), as approximately 50% of the patients develop cutaneous mycotic infections. Because superficially infected fungi in the stratum corneum of the epidermis cannot directly contact with T cells infiltrating in the upper dermis, some perturbation of epidermal innate immunity has been postulated. Interleukin (IL)-17-producing helper T cells (Th17) can induce the keratinocyte production of antimicrobial peptides such as human beta defensin (HBD)-2 and LL-37, which play an essential role in cutaneous innate immunity. Experimental Design: We investigated the frequency of circulating Th17 cells, serum levels of cytokines, and epidermal expression of HBD-1, 2, 3, and LL-37 in ATLL patients with or without superficial dermatophytosis. Results: The frequency of peripheral Th17 cells and the serum level of IL-17 was significantly decreased in ATLL patients, whereas the serum IL-10 and TGF-beta 1 levels were increased as compared with healthy controls. Furthermore, ATLL patients with dermatophytosis had higher IL-10 and TGF-b1 levels and lower IL-17 levels than did those without dermatophytosis. Immunohistochemical study revealed that the epidermal expression of both HBD-2 and LL-37 were significantly lower in ATLL patients with dermatophytosis than in non-ATLL patients with dermatophytosis. Conclusions: Taken together, these results suggest that the keratinocyte production of antimicrobial peptides promoted by Th17 cells is reduced in ATLL patients, leading to the perturbed innate immunity and the frequent occurrence of superficial dermatophytosis. Clin Cancer Res; 18(14); 3772-9. (C)2012 AACR.