Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 Immunity as Cornerstone of Non-alcoholic Fatty Liver Disease: The Contribution of Innate and Adaptive Immune Mechanisms in the Pathogenesis of the Metabolic Syndrome-related Steatohepatitis 1 19 Danxi Wang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Renxia Zhang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Huili Huang Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China Ling Yin Department of Infectious Diseases, The Second Affiliated Hospital of Naval Medical University, Shanghai, China 2025 05 20 2025 09 12 Non-alcoholic fatty liver disease (NAFLD) is a major hepatic manifestation of metabolic syndrome and encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). This study aimed to evaluate the contribution of immunological, inflammatory, and metabolic parameters-including cytokine levels, immune cell profiles, and microRNA (miR) expression-in the progression from NAFLD to NASH among individuals with features of metabolic syndrome. An observational study was conducted between January 2022 and December 2024, enrolling 300 adult patients with radiologically or histologically confirmed NAFLD. Patients underwent comprehensive anthropometric, biochemical, and immunological assessments, including cytokine profiling (interleukin [IL]-6, IL-17, tumor necrosis factor-α [TNF-α], transforming growth factor-β1 [TGF-β1]), immune cell phenotyping (T helper 17 [TH17], regulatory T cells [Tregs], monocytes), and miR quantification (miR-122, miR-34a). Liver biopsy was performed in 95 selected cases.. The nursing team also assists in coordinating multidisciplinary care and ensuring follow-up compliance, which are vital for long-term disease management and reducing progression to NASH. Significant elevations were observed in metabolic parameters (body mass index [BMI], homeostatic model assessment for insulin resistance [HOMA-IR]), hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], ferritin), and oxidative stress markers (malondialdehyde [MDA]). Adipokines (↑leptin, ↓adiponectin), hepatokines (↑fibroblast growth factor 21 [FGF21], ↑fetuin-A), and cytokines (↑IL-6, ↑TNF-α, ↑IL-17) were markedly altered in patients with biopsy-proven NASH. This study reinforces that pro-inflammatory cytokines, altered immune cell profiles, and dysregulated miRs serve as promising biomarkers for early identification and potential therapeutic targeting in metabolic syndrome-associated steatohepatitis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4449 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4449/2285