Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 01 17 1 10 Mohsen Ghoryani Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran Soroush Gorgani Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mahdi Atabaki Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Elmira Noori Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Zhaleh Shariati-Sarabi Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mojgan Mohammadi Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran 2025 10 17 2025 11 09 Osteoarthritis (OA) is the most common form of arthritis, characterized by pathological changes in joint components. Increasing evidence suggests that helper T (TH) lymphocytes play a pivotal role in the inflammatory processes associated with OA. Curcumin, the primary polyphenolic compound found in Curcuma longa, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of curcumin on the gene expression of key transcription factors of TH1 and TH2 cells and to explore their associations with clinical and immunological parameters in patients with knee OA. This mechanistic sub-study presents a secondary molecular analysis of RNA biospecimens from a previously completed double-blind, placebo-controlled clinical trial involving 30 patients with knee OA. Participants were randomly assigned to receive either 80 mg/day of nano-micelle curcumin or a placebo for 3 months. Expression levels of T-box transcription factor 21 (T-bet) and GATA binding protein 3 (GATA3), the key transcription factors of TH1 and TH2 cells, respectively, were quantified using SYBR Green-based real-time PCR. Their associations with changes in visual analogue scale (VAS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and percentages of CD4+ and CD8+ T cells were analyzed. Curcumin administration significantly reduced T-bet gene expression compared to baseline and showed a positive correlation with the frequency of CD8+ T cells, while GATA3 expression remained unchanged. These findings may provide a novel molecular perspective on curcumin's potential to influence CD8+ T cell dynamics by modulating TH1-associated transcriptional programs. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4633 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4633/2284