Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 197 220 EN Mohsen Rokni Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Maryam Akhtari Tobacco Prevention and Control Research Center (TPCRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Elham Madreseh Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Samaneh Enayati Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mina Sadeghi Shaker Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Shayan Mostafaei Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Farhad Gharibdoost Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Mohammad Vodjgani Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2023 10 30 2024 01 02 Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3941 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3941/2021