Regulation of thymus and thymopoiesis by thyroid hormones and corticosteroids: Insights from vertebrate metamorphosis.

In vertebrates, the thymus is maximally active during the early life, when it coordinates the T cell developmental proceedings with the environmental cues to generate a pool of T cells responsible for life-long immunity. Apart from cytokines and growth factors, hormones play a pivotal role in bridging the thymic microenvironment with the external and internal macroenvironment of the host during the early life. The post-embryonic life in lower vertebrates (like fish and amphibians) involves a period of radical physiological remodeling, known as metamorphosis. Two endocrine axes: the thyroid hormones and the corticosteroids, cardinally regulate most of the physico-chemical changes during metamorphosis in these organisms. Functional execution of these signaling axes enables continuous integration of macro- and microenvironmental signals with the core genetic circuitry of development during the window of metamorphosis. As part of the coping strategies against the holistic eco-physiological changes during metamorphosis, the immune system, including the thymus, undergoes drastic changes in structure and function. However, there is a dearth of consolidated perspectives regarding the influence of these hormones on the metamorphosis-associated remodeling of the thymus and thymopoiesis, limiting our understanding of the most primitive and rudimentary forms of endocrine regulation over post-embryonic and perinatal thymopoiesis in vertebrates. This review chronicles the influence of these hormones on thymus formation, remodeling and thymopoiesis during metamorphosis in fish and amphibians, and traces their evolutionary conservation in higher vertebrates, which undergo direct, continuous development instead of metamorphosis. Insights emerging from this review might be pivotal for the conceptualization of the primitive forms of endocrine regulation over the thymus and thymopoiesis. Furthermore, the concepts might yield important clues about the evolutionary tuning of the growth-degeneration-regeneration cycle of the thymus as well as thymus-dependent immunity to endocrine pulsations during the early life in vertebrates.