Immunoregulation by DC and T cells in psoriasis with probable immunotherapeutic approaches

Psoriasis is a chronic, immune-mediated inflammatory disorder with systemic implications beyond its cutaneous manifestations. Its pathogenesis involves a complex interplay between genetic predisposition, environmental triggers, and immune dysregulation. The sustained crosstalk between dendritic cells (DCs) and T cells, which orchestrates the initiation and perpetuation of psoriatic inflammation. Plasmacytoid DCs, activated by nucleic acid-LL37 complexes, produce interferon-α that promotes myeloid DC maturation. These DCs secrete IL-12, IL-23, and TNF-α, driving differentiation of naïve T cells into Th1, Th17, and Th22 subsets. Effector T cells subsequently release cytokines such as IFN-γ, IL-17, and IL-22, which promote keratinocyte hyperproliferation, impaired differentiation, neutrophil recruitment, and angiogenesis. This DC-T cell axis forms a self-amplifying inflammatory loop that underpins disease chronicity. Conventional systemic agents, including methotrexate, cyclosporine, and retinoids, have demonstrated efficacy but are limited by nonspecific immunosuppression and significant toxicities. Advances in immunology have identified the IL-23/Th17 pathway as a pivotal therapeutic target, enabling the development of biologics and small-molecule inhibitors. Monoclonal antibodies targeting TNF-α, IL-12/23, IL-17, and IL-23 have revolutionized management, achieving high rates of sustained clearance with improved safety profiles. Additional strategies, such as PDE4 and JAK/STAT inhibitors, offer oral alternatives with targeted immunomodulation. Novel approaches, including tolerogenic DC therapy and neuroimmune modulation, hold promise for refining treatment and addressing disease heterogeneity. Effective immunotherapeutic strategies must therefore balance skin clearance with reduction of systemic inflammation and long-term comorbidity risk. Integrating mechanistic insights into DC-T cell interactions with emerging therapies provides a framework for personalized, safer, and more durable disease control.