Targeting Molecular Dysregulation in Ulcerative Colitis: A Paired Cellular Perspective on CD4⁺, CD8⁺, and IL-6 Immunohistochemistry

Histological healing is increasingly recognized as a sensitive marker of disease remission in ulcerative colitis (UC). However, the dynamics of mucosal T lymphocytes and proinflammatory cytokines during healing remain incompletely understood. In this paired, within-subject observational study (retrospective analysis of paired biopsies), colonic biopsy sets from 20 adult UC patients were analyzed during active inflammation and at a subsequent time point of 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. Histological activity was assessed using the Geboes score. Intraepithelial CD4⁺ T cells significantly decreased during histologic healing (mean 6.8 → 3.75 cells/100 epithelial cells, 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. Histologic healing in UC involves compartment-specific shifts in T lymphocyte populations and a marked reduction in 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.