Immunoregulation

Immunoregulation is the set of processes that regulate the magnitude, duration, and quality of immune responses in order to protect the host from infection while limiting tissue damage and maintaining immune homeostasis. It encompasses both central tolerance, which eliminates or edits self-reactive lymphocytes during development, and peripheral tolerance, which restrains mature cells in tissues and circulation.

Key cellular mediators include regulatory T cells (often CD4+FOXP3+), regulatory B cells, tolerogenic dendritic cells, and myeloid-derived suppressor cells, as well as various macrophage phenotypes. These cells act through contact-dependent mechanisms and secreted factors to dampen activation, promote anergic states, or induce apoptosis in effector cells. Important molecular mediators and checkpoints include cytokines such as interleukin-10 and transforming growth factor-beta, as well as immune checkpoint pathways like CTLA-4 and PD-1/PD-L1.

Mechanistically, immunoregulation operates by deleting or inactivating self-reactive clones, actively suppressing responses to non-self, and promoting tolerance to harmless antigens such as food or commensal microbes. The balance between activation and regulation is influenced by the tissue context, microbial signals, and neuroendocrine signals, and it can be altered in disease.

Disruptions of immunoregulation are associated with autoimmunity, chronic infections, immunodeficiency, and allergies, while enhanced regulation can contribute to tolerance in transplantation and, in the tumor microenvironment, to immune evasion by cancer. Therapeutic strategies aim to modulate regulatory pathways to restore balance.