Immune System Modulation by Thyroid Axis Includes Direct Genomic and Nongenomic Actions of Thyroid Hormones on Immune Cells

A bidirectional circuit exists between the neuroendocrine and immune systems that functions to maintain and protect the internal homeostasis of the organism. In this context, interactions between thyroid hormones (TH) and the immune system are revealed mainly by the presence of specific receptors for TH on lymphocytes or by the frequent immune alterations associated with physiological or pathological fluctuations of TH. In this context, both hypothyroidism in humans and experimentally-induced hypothyroidism in rodents have been shown to diminish thymus activity, to lead to spleen and lymph node involution and to depress humoral and cell-mediated immune responses. All these effects are reversed by restoration of the euthyroid state. In contrast, in vivo up-regulation of TH levels, but not those of thyrotropic hormones, leads to an increase in lymphocyte reactivity and an increment of inflammatory and T-cell derived cytokines. Additionally, TH direct actions on T lymphocytes were recently demonstrated as well, showing that TH are able to increase T cell proliferation through the activation of both nongenomic and genomic intracellular signals. These actions point to the important role that these hormones play in regulating lymphocyte function. Additional studies are needed of the mechanisms involved in cellular interactions within the immunoneuroendocrine network, as well as the consequences of their alterations. Such studies may disclose contributions of TH to the pathophysiology of the immune system and thus suggest novel approaches to modulation of immunopathology via manipulation of endogenous TH.