title: Decreased expression of IL-27 in moderate-to-severe psoriasis and its anti-inflammation role in imiquimod-induced psoriasis-like mouse model.
abstract: BACKGROUND
  Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive.
  
  
  OBJECTIVE
  The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Th1 and Th17.
  
  
  METHODS
  IL-27 and IL-27 receptor α (IL-27Rα) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasis mouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-γ in serum and skin lesion.
  
  
  RESULTS
  The expression levels of IL-27 and IL-27Rα were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL-17A level in serum and psoriasis-like lesion in the IMQ-treated mice.
  
  
  CONCLUSIONS
  Our results suggest that IL-27 might predominantly play a protective role in the pathogenesis of psoriasis through abrogating Th17 differentiation. The potential therapeutic benefit of harnessing IL-27 in treating psoriasis awaits future investigation.
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Chengwen
authors.initials: C
authors.lastname: Fei
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: shiyuling1973@tongji.edu.cn.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077271:Imiquimod; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D000634:Aminoquinolines; C000611649:IFNG protein, mouse; C508609:IL10 protein, human; C112441:IL27RA protein, human; C098680:Il17a protein, mouse; D020381:Interleukin-17; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D000077271:Imiquimod
keywords: IL-27; Imiquimod; Psoriasis; Th17