Abnormal expression of interleukin-23 in mycosis fungoides/Sézary syndrome lesions

Abstract

Progression of mycosis fungoides (MF) to Sézary syndrome (SS) is accompanied by a shift from a T(H)1 to a T(H)2 cytokine profile. Interleukin (IL)-23 is a novel cytokine that shares a common p40 subunit with the T(H)1 inducer, IL-12. IL-23 induces a third profile, T(H)IL-17, that is dominant in inflammation and autoimmunity. Although IL-23 induces an eczematous-like skin reaction in mice, and is expressed in T(H)1-mediated skin disorders such as psoriasis, it has not been evaluated in MF/SS. To study the role of IL-23 in MF/SS development, 40 MF/SS lesions of all stages were immunohistochemically analyzed with a novel anti-human IL-23 antibody raised against full-length human IL-23. IL-23 was detected with the catalyzed signal amplification system. The intensity and frequency of IL-23 staining were semi-quantitatively graded in both the dermal infiltrate and the epidermis. Increased expression of IL-23 was observed throughout the epidermal keratinocytes and in dermal lymphocytes compared to normal skin. IL-23 intensity did not differ significantly among the stages of MF/SS; however, in stage IVB patients, we observed lower frequency of IL-23 expression in dermal lymphocytes than in other stage patients [P = 0.13, analysis of variance (ANOVA)]. Interestingly, clusters of atypical lymphocytes, especially the epidermotropic tumor cells, demonstrated weak or absent IL-23 staining in 18 of 40 (45%) lesions. This finding was present in 4 of 5 (80%) of the stage IVB lesions and 7 of 11 (64%) of the lesions from Sézary patients. These findings indicate that abnormal IL-23 expression may play a role in the pathogenesis and progression of MF/SS.

The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders

“…This result further supports the notion that C-ALCL and LyP (type C) have overlapping histologic features and may be closely related. In agreement with our findings, earlier studies have reported MUM1 expression in 80% to 100% of ALCL [7,8,19]. Unfortunately, these authors did not indicate whether S-ALCL or C-ALCL was included in their studies.…”

“…Our data confirm and extend the observations reported in the prior studies [4,19,20]. The expression of MUM1 in T-cell lymphoproliferative disorders other than ALCL suggests that this protein may play a role in regulating a much larger spectrum of lymphoid processes than was previously recognized.…”

“…Doherty et al [19] observed weak or absent IL-23 staining among the epidermotropic tumor cells in stage IVB MF and SS. Li et al [21] found p53 overexpression in the large cells of LCT, although this expression was not associated with a p53 gene mutation.…”

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

“…Some studies have reported IL-17 mRNA and/or protein expression in situ and ex vivo, whereas others reported its absence, despite the presence of IL-22-producing Th17-like cells. 21,[57][58][59]60 The present findings offer a possible explanation for these opposing results; specifically, that the differences in frequency and severity of skin colonization and infection by SE-producing bacteria between different cohorts of patients and even within a single cohort may explain why IL-17 expression differed between these studies and between patients within a single cohort. 21,57,60 The finding that SEA induces IL-17 expression in nonmalignant primary T cells was not unexpected, given that SEA mediates STAT3 activation in these cells, 77 but it was important because it suggests that both malignant and nonmalignant T cells may contribute to IL-17 expression in vivo.…”

Specific IgE toward Allergenic Molecules Is a New Prognostic Marker in Patients with Sézary Syndrome

“…2b). With regard to this, several studies suggested a skewed Th2 cytokine profile in SS strongly related to the presence of a circulating malignant CD4+ T cell clone with Th2 features [7,8,14,55,56,57]. It is widely known that IgE production is the result of Th2-skewed immune response, but also the presence of CD60 on T cells has been recently associated with functional Th2 profile [58,59].…”