Abnormal expression of interleukin-23 in mycosis fungoides/Sézary syndrome lesions.
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.
Doherty
Sean D
SD
Department of Dermatology, M.D. Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Ni
Xiao
X
Doherty
Christy B
CB
Jones
Dan
D
Zhao
Xing
X
Owen
Laurie B
LB
Duvic
Madeleine
M
D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D009182:Mycosis Fungoides / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012751:Sezary Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology; D018418:Th2 Cells / Q000473:pathology
D053759:Interleukin-23