title: Analysis of the IL-31 pathway in Mycosis fungoides and Sézary syndrome.
abstract: IL-31, predominantly produced by CD45RO + CLA + Th2 cells, plays an important pathogenetic role in pruritic skin diseases like atopic dermatitis. As tumor cells in Sézary syndrome (SS) and Mycosis fungoides (MF) possess similar immunophenotypes and the conditions mentioned are often associated with pruritus, the analysis of the IL-31 pathway in MF/SS patients is of interest. Serum samples from the peripheral blood of 23 patients and 17 controls were analyzed for IL-31 abundance and correlated with disease stage and pruritus. Furthermore IL-31-, IL-31 receptor alpha (IL-31Rα)- and Oncostatin M receptor beta (OSMRβ)-mRNA expression was measured in blood tumor cells from SS patients, memory T-cells from controls and lymphoma cell lines. Serum IL-31 levels were low but differed between groups with no or strong pruritus. Expression of IL-31 was detectable at low levels in cell lines, but not in the tumor cells of SS patients. Stimulation with PMA/ionomycin led to indiscriminate expression in peripheral blood tumor cells and control T-cells. IL-2-stimulation resulted in expression only in 9/11 patient samples. IL-31Rα-expression was detectable in 10/10 cell lines, 8/15 peripheral blood samples from SS patients, and 4/10 controls; whereas, OSMRβ mRNA was detectable in 4/10 cell lines, but only one patient and control sample. The results of our analyses regarding serum levels and receptor expression do not suggest a central role of IL-31 in MF/SS pathogenesis. However, the results of IL-2 stimulation as well as the increased IL-31 levels in patients with strong pruritus offer a rationale for therapeutic approach in this subset of patients.
authors.affiliation: Department of Dermatology and Allergy, Skin cancer centre Charité, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gryzik
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haidar
authors.forename: Daniel
authors.initials: D
authors.lastname: Humme
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.forename: Staffan
authors.initials: S
authors.lastname: Vandersee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood* / Q000235:genetics; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012751:Sezary Syndrome / Q000097:blood* / Q000235:genetics; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000097:blood* / Q000235:genetics
chemical_list: C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin