Immunregulation

Immunoregulation refers to the processes that control and balance the immune system's responses to prevent excessive inflammation and tissue damage while preserving ability to defend against pathogens. It operates at multiple levels, including central tolerance in primary lymphoid organs and peripheral tolerance in secondary sites, and adapts to the physiological context of infection, vaccination, pregnancy, and aging.

Key cellular mediators include regulatory T cells (CD4+ CD25+ FOXP3+), regulatory B cells, tolerogenic dendritic cells, and myeloid-derived suppressor cells. Other cell types can contribute to regulation, such as regulatory macrophages and certain Th cell subsets (e.g., Tr1, Th3). Cytokines such as interleukin-10, transforming growth factor-beta, and interleukin-35, as well as metabolic pathways (adenosine signaling via CD39 and CD73), contribute to suppressive milieus. Immune checkpoints, including CTLA-4 and PD-1, help restrain T cell activity.

Mechanisms of regulation include inhibition of effector T cell activation and proliferation, suppression of helper B cell responses, induction of T cell anergy or deletion, alteration of antigen presentation, and metabolic disruption of immune cells. These processes promote tolerance to self-antigens and to non-harmful environmental antigens, and they tailor responses to ongoing challenges to minimize collateral damage.

Clinical relevance: dysregulation can lead to autoimmunity, allergy, or chronic infections; conversely, boosting immunoregulation is a strategy in transplantation and autoimmune disease management, while dampening regulatory pathways is a strategy in cancer immunotherapy. Therapeutic approaches include cytokine modulation, cell-based regulatory therapies, and immune checkpoint targeting.