TY - JOUR
T1 - Abnormal expression of interleukin-23 in mycosis fungoides/Sézary syndrome lesions
AU - Doherty, Sean D.
AU - Ni, Xiao
AU - Doherty, Christy B.
AU - Jones, Dan
AU - Zhao, Xing
AU - Owen, Laurie B.
AU - Duvic, Madeleine
N1 - Funding Information:
Acknowledgments This study was funded in part by NCI K24 CA86815 (MD), CA16672, and the Sherry L. Anderson Patient Research Fund.
PY - 2007/12
Y1 - 2007/12
N2 - Progression of mycosis fungoides (MF) to Sézary syndrome (SS) is accompanied by a shift from a TH1 to a TH2 cytokine profile. Interleukin (IL)-23 is a novel cytokine that shares a common p40 subunit with the TH1 inducer, IL-12. IL-23 induces a third profile, THIL-17, that is dominant in inflammation and autoimmunity. Although IL-23 induces an eczematous-like skin reaction in mice, and is expressed in TH1-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.
AB - Progression of mycosis fungoides (MF) to Sézary syndrome (SS) is accompanied by a shift from a TH1 to a TH2 cytokine profile. Interleukin (IL)-23 is a novel cytokine that shares a common p40 subunit with the TH1 inducer, IL-12. IL-23 induces a third profile, THIL-17, that is dominant in inflammation and autoimmunity. Although IL-23 induces an eczematous-like skin reaction in mice, and is expressed in TH1-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.
KW - Cutaneous T-cell lymphoma
KW - Interleukin-23
KW - Mycosis fungoides
UR - http://www.scopus.com/inward/record.url?scp=33751193443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751193443&partnerID=8YFLogxK
U2 - 10.1007/s00403-006-0705-x
DO - 10.1007/s00403-006-0705-x
M3 - Article
C2 - 17021762
AN - SCOPUS:33751193443
SN - 0340-3696
VL - 298
SP - 353
EP - 356
JO - Archives of Dermatological Research
JF - Archives of Dermatological Research
IS - 7
ER -