Maryam ALADODO, Saheed Ayodeji ADEKOLA, Habeebat Abiola SULEIMAN, Abdulrahman Gbenga ABDULMUMIN, Rasheedat O. BABA, Raliat Abimbola ALADODO
Turkish Journal of Immunology - 2026;14(2):59-74
The immune system sustains health through a carefully calibrated equilibrium between activation and restraint, a balance that, when disrupted, gives rise to a clinically heterogeneous spectrum of disorders collectively termed immune dysregulation. Spanning autoimmune diseases, primary and secondary immunodeficiencies, hypersensitivity reactions, and chronic inflammatory states, these conditions collectively affect hundreds of millions of people globally and impose an enormous burden on healthcare systems as well as individual quality of life. Central to the pathophysiology of nearly all immunological disorders is the failure of immune tolerance, including both the thymic mechanisms that eliminate autoreactive lymphocytes during development and the peripheral checkpoints, including regulatory T cells (Tregs), co-inhibitory molecules, and cytokine circuits, that restrain self-reactive clones escaping central deletion. Beyond tolerance failure, immune dysregulation emerges through a convergence of genetic mutations affecting key regulatory genes (e.g., FOXP3, AIRE, RAG, and IL10), epigenetic reprogramming driven by environmental exposures, microbial dysbiosis, and perturbations in cytokine networks. The clinical consequences range from organ-specific destruction in type 1 diabetes mellitus and multiple sclerosis (MS) to life-threatening systemic syndromes including cytokine storm and multi-organ failure. Current therapeutic strategies, including immunomodulatory drugs, biological agents, Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), and emerging chimeric antigen receptor T (CAR-T)-cell approaches, have transformed outcomes but fall short of providing a cure for most conditions. This review synthesizes the current mechanistic understanding, maps the clinical landscape of immune dysregulation, critically evaluates the evidence for existing and novel therapies, and identifies key gaps where future research must focus to achieve disease-modifying and curative outcomes.
