Immunopathogenesis and immunoregulatory mechanisms in allergic contact dermatitis

Allergic contact dermatitis (ACD) is a common inflammatory skin disorder characterized as a T cell-mediated delayed-type hypersensitivity reaction induced by cutaneous exposure to haptens. Its pathogenesis unfolds through three distinct phases: sensitization, elicitation, and resolution. During sensitization, hapten-modified proteins are processed by dendritic cells, particularly Langerhans cells and dermal dendritic cells, which migrate to lymph nodes to prime naive T cells. Pattern recognition receptors, including Toll-like receptors and the NLRP3 inflammasome, critically regulate this innate-adaptive interface. The elicitation phase involves hapten-specific Th1 and Th17 cells orchestrating inflammation through cytotoxicity and cytokine release. Conversely, resolution relies on regulatory T cells and IL-10 and TGF-beta signaling to restore tissue homeostasis. Emerging immunomodulators such as vitamin D exhibit dose-dependent regulatory effects potentially influenced by sex-specific factors and U-shaped associations. Despite significant advances, critical gaps persist regarding tissue-resident memory T cells and precise sensitization thresholds. Integrating immunology, neurobiology, and metabolomics may advance precision therapies targeting pathways like NLRP12 or ultraviolet-induced vitamin D synthesis. This review summarizes current progress in elucidating the immunopathogenesis of ACD and highlights emerging mechanisms that may support the development of more precise and effective therapeutic strategies.