title: The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis.
abstract: OBJECTIVE
  The objective was to survey the expression and localization of Th17-related cytokines and their correlation with skin lesion severity in early systemic sclerosis (SSc).
  
  
  METHODS
  The mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) from 21 SSc patients and 12 healthy controls (HC). The protein expression was examined by immunohistochemistry (IHC) and Western blotting.
  
  
  RESULTS
  The RT-qPCR analysis showed a significantly higher expression of IL-17A, IL-21, IL-22, IL-26, IL-17RA, IL-21R, and IL-22R1 mRNA; consistently, the IHC analysis showed an over-expression of IL-17RA, IL-21R and IL-22R1 and the Western blotting analysis showed an over-expression of IL-17A, IL-21, IL-21R and IL-22R1 in early SSc skin lesions. The mRNA levels of IL-21 were higher in diffuse cutaneous than limited cutaneous SSc lesions. The mRNA expression of IL-26, IL-22, IL-22R1, mRNA and protein expression of IL-17A, IL-21, IL-21R were positively correlated with the modified Rodnan skin score of SSc. In addition, the mRNA levels of ICAM-1 were positively correlated with IL-17A/IL-17RA, and VEGFA and IL-4 were both positively correlated with IL-21/IL-21R, while TGF-β were moderately negatively correlated with IL-22/IL-22R1.
  
  
  CONCLUSIONS
  Th17 cytokines contribute to progression in early SSc skin lesions. IL-21/IL-21R could act as potential biomarkers presenting early SSc skin lesions severity.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Medicine College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Bone and Joint Diseases, Xi'an Honghui Hospital, Nanguo Road 76, Xi'an, Shaanxi 710054, China.
authors.forename: Weikun
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Bone and Joint Diseases, Xi'an Honghui Hospital, Nanguo Road 76, Xi'an, Shaanxi 710054, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Medicine College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
authors.forename: Congshan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Medicine College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Kuanhou
authors.initials: K
authors.lastname: Mou
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China.
authors.forename: Liesu
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Genetics and Molecular Biology, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, China. Electronic address: shemin.lu@gmail.com.
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D042241:Early Diagnosis; D005260:Female; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D018799:Intercellular Adhesion Molecule-1; D020381:Interleukin-17; D053738:Interleukin-21 Receptor alpha Subunit; D015847:Interleukin-4; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000097043:Interleukin-22; D000098546:Interleukin-21; C573420:ICAM1 protein, human; C508717:IL17A protein, human; C109985:IL17RA protein, human; C508117:IL21R protein, human; C406767:IL26 protein, human; C508598:IL4 protein, human; C467484:VEGFA protein, human; C415369:interleukin-22 receptor
keywords: Skin lesion; Systemic sclerosis; Th17