Yan Zhou1, Weikun Hou2, Ke Xu2, Dan Han3, Congshan Jiang4, Kuanhou Mou3, Yue Li4, Liesu Meng4, Shemin Lu5. 1. 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. 2. Department of Bone and Joint Diseases, Xi'an Honghui Hospital, Nanguo Road 76, Xi'an, Shaanxi 710054, China. 3. Department of Dermatology, The First Affiliated Hospital of Medicine College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. 4. 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. 5. 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.
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.
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: Tiago Carvalheiro; Alsya J Affandi; Beatriz Malvar-Fernández; Ilse Dullemond; Marta Cossu; Andrea Ottria; Jorre S Mertens; Barbara Giovannone; Femke Bonte-Mineur; Marc R Kok; Wioleta Marut; Kris A Reedquist; Timothy R Radstake; Samuel García Journal: Arthritis Rheumatol Date: 2019-08-27 Impact factor: 10.995