Thyroid Hormones and Immune Regulation: Molecular Mechanisms and Clinical Implications of Endocrine–Immune Cross-Talk

Abstract

The immune and endocrine systems function together to keep the body in balance through regulating mechanisms alongside the body's capacity to respond to both internal and external stressors. The two principal thyroid hormones are T4 (thyroxine) and T3 (triiodothyronine); both are widely recognized as having critical roles in managing an individual’s metabolism, growth, and energy levels. Current literature indicates that thyroid hormones are also important regulators of the immune system. Thyroid hormones play a role in the development, differentiation, and function of immune cells. Investigating the molecular pathways that inform the relationship between thyroid hormones and the immune system will provide insight into the etiology of immune-mediated diseases and other systemic/pathophysiological processes. The aim of the current narrative review is to determine what is known based on the scientific literature regarding how thyroid hormones impact the immune system on a molecular level, as well as how these effects could influence the clinical presentation of immune-mediated and systemic disease. A narrative review of the literature was performed using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant publications. This review summarizes current evidence regarding the molecular mechanisms through which thyroid hormones regulate immune function and how immune activation influences thyroid physiology. Evidence from experimental and clinical studies indicates that thyroid hormones modulate innate and adaptive immunity through genomic and non-genomic pathways involving thyroid hormone receptors, MAPK, PI3K/Akt, and NF-κB signaling. Conversely, inflammatory cytokines alter thyroid hormone metabolism and contribute to non-thyroidal illness syndrome. These interactions are implicated in autoimmune thyroid disease, infection, sepsis, cancer progression, and responses to immunotherapy. Understanding endocrine–immune cross-talk may improve diagnostic strategies and support the development of targeted therapeutic approaches