The interdependence between thyroid hormones (THs), namely, thyroxine and triiodothyronine, and immune system is nowadays well-recognized, although not yet fully explored. Synthesis, conversion to a bioactive form, and release of THs in the circulation are events tightly supervised by the hypothalamic–pituitary–thyroid (HPT) axis. Newly synthesized THs induce leukocyte proliferation, migration, release of cytokines, and antibody production, triggering an immune response against either sterile or microbial insults. However, chronic patho-physiological alterations of the immune system, such as infection and inflammation, affect HPT axis and, as a direct consequence, THs mechanism of action. Herein, we revise the bidirectional crosstalk between THs and immune cells, required for the proper immune system feedback response among diverse circumstances. Available circulating THs do traffic in two distinct ways depending on the metabolic condition. Mechanistically, internalized THs form a stable complex with their specific receptors, which, upon direct or indirect binding to DNA, triggers a genomic response by activating transcriptional factors, such as those belonging to the Wnt/β-catenin pathway. Alternatively, THs engage integrin αvβ3 receptor on cell membrane and trigger a non-genomic response, which can also signal to the nucleus. In addition, we highlight THs-dependent inflammasome complex modulation and describe new crucial pathways involved in microRNA regulation by THs, in physiological and patho-physiological conditions, which modify the HPT axis and THs performances. Finally, we focus on the non-thyroidal illness syndrome in which the HPT axis is altered and, in turn, affects circulating levels of active THs as reported in viral infections, particularly in immunocompromised patients infected with human immunodeficiency virus.

甲状腺激素（TH）（即甲状腺素和三碘甲状腺原氨酸）与免疫系统之间的相互依赖性现已得到充分认识，但尚未得到充分探索。TH 的合成、转化为生物活性形式以及循环中 TH 的释放均受到下丘脑-垂体-甲状腺 (HPT) 轴的严格监督。新合成的 TH 诱导白细胞增殖、迁移、细胞因子释放和抗体产生，引发针对无菌或微生物损伤的免疫反应。然而，免疫系统的慢性病理生理改变，例如感染和炎症，会影响 HPT 轴，并直接影响 TH 的作用机制。在此，我们修改了 TH 和免疫细胞之间的双向串扰，这是在不同环境下正确的免疫系统反馈反应所必需的。可用的循环 TH 根据代谢状况以两种不同的方式进行运输。从机制上讲，内化的 TH 与其特定受体形成稳定的复合物，该复合物在直接或间接与 DNA 结合后，通过激活转录因子（例如属于 Wnt/β-连环蛋白途径的转录因子）来触发基因组反应。或者，TH 与细胞膜上的整合素 αvβ3 受体结合并触发非基因组反应，该反应也可以向细胞核发出信号。此外，我们重点介绍了 THs 依赖性炎性体复合物调节，并描述了在生理和病理生理条件下 THs 参与 microRNA 调节的新关键途径，这些途径改变了 HPT 轴和 THs 的性能。最后，我们关注非甲状腺疾病综合征，其中 HPT 轴发生改变，进而影响病毒感染中活性 TH 的循环水平，特别是在感染人类免疫缺陷病毒的免疫功能低下患者中。