Targeting Molecular Dysregulation in Inflammatory Bowel Disease: A Cellular Perspective

Background: Histologic healing is increasingly recognized as a sensitive marker of disease remission in ulcerative colitis (UC). However, the dynamics of mucosal T lymphocytes and pro-inflammatory cytokines during healing remain incompletely understood. Methods: In this observational, cross-sectional study, paired colonic biopsies from 20 adult UC patients were analyzed during active inflammation and subsequent histologic healing. Immunohistochemistry was performed for CD3, CD4, CD8, and IL-6. Lymphocyte densities were quantified in intraepithelial and lamina propria compartments, while IL-6 expression was scored semi-quantitatively. Histologic activity was assessed using the Geboes score. Results: Intraepithelial CD4⁺ T cells significantly decreased during histologic healing (mean 6.8 → 3.75 cells/HPF, p < 0.05), whereas lamina propria CD4⁺ cells remained variably persistent, suggesting ongoing immune regulation. Intraepithelial CD8⁺ cells increased during remission, indicating a potential reparative or surveillance role. IL-6 expression markedly declined in epithelial and stromal compartments during healing, reflecting resolution of mucosal inflammation. Correlation analyses revealed enhanced coordination between CD4⁺ and CD8⁺ cells in the healing phase, consistent with immune homeostasis. Conclusions: Histologic healing in UC involves compartment-specific shifts in T lymphocyte populations and a marked reduction of IL-6 expression, reflecting coordinated immune regulation beyond clinical remission. These findings highlight the potential of combined cellular and cytokine biomarkers to monitor mucosal healing and guide immunomodulatory therapies.