T helper 1-related molecules as well as IL-15 are hyperexpressed in the skin lesions of patients with pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Whether a number of studies confirmed the central role of innate immunity, only few studies investigated the possible contributing role of acquired immunity. In particular, no reports about Th1 and Th2 cells are available yet. Therefore, 15 patients with PG, 5 with Sweet's syndrome (SS) and 9 skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers IL-12, IFN-γ, CXCR3, CCR5, of the Th2 related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40L, of IL-15 and the NK cell marker CD56 in skin lesions by immunohistochemistry. Patients with PG and SS showed a higher expression of Th1 markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous in PG skin lesions compared to SS ones (p=0.0157 and <0.0001, respectively). Both CD40 and CD40L were more expressed in PG than in SS and HC (p<0.0001 for both). Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients with PG than in those of SS and HC (p<0.0001 for both). Our results suggested that Th2 cells are downregulated in PG. At the same time, the overexpression of the co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance. Both these findings might explain the most aggressive behaviour of PG in comparison to SS. Moreover, the overexpression of IL-15 and CD56+ may suggest a possible role of NK-cells in the pathogenesis of the disease..