Developmental thyroid disruption causes long-term impacts on immune cell function and transcriptional responses to pathogen in a small fish model

Abstract

Current evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from < 1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood (5–7 months post hatch) at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases (1.2-fold) in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load or pathogen resistance were noted. Overall, these results suggest that early life stage TH suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development, which can occur in response to chemicals present in the environment, may have lasting effects on immune function in adulthood.

Late gestation fetal hypothyroidism alters cell cycle regulation across multiple organ systems

“…In the developing fetus, immature T cells, known as thymocytes, migrate to the THY to undergo maturation into functional T cells [ 54 ], while the SPLN aids in the maturation and proliferation of B cells [ 55 ]. Previous research in rats [ 56 ] and fish [ 57 ] has shown that treatment with antithyroid drugs modulates immune function in developing animals, suggesting that thyroid hormones are essential for SPLN and thymic fetal development. In our study, we observed an increase in CDKN1A expression in the SPLN and THY of MMI-treated fetuses, which could be indicative of reduced proliferation that has the potential to weaken the postnatal adaptive immune response, further corroborating the important role of thyroid hormones in immune system development.…”

Hashimoto’s thyroiditis increases the risk of new-onset systemic lupus erythematosus: a nationwide population-based cohort study

“…Thus, the common presence of ANA in patients with HT might be a crucial factor to induce the development of SLE. Last, studies have shown that phagocytosis was stimulated by physiological concentrations of thyroid hormone [ 30 ], and it was decreased after thyroid suppression in an animal model [ 31 ]. It means HT patients with hypothyroidism might lose the ability to clean up the autoimmune complex and develop SLE [ 32 ], which might explain why patients with hypothyroidism have a higher risk of SLE than hyperthyroidism in our study.…”

Phoenixin-14 alters transcriptome and steroid profiles in female green-spotted puffer (Dichotomyctere nigroviridis)

“…Data were expressed as mean ± standard error, and log-transformed relative expression levels were analyzed using two sample t tests in SYSTAT12 (Systat Software Inc., San Jose, CA, USA) and assessed at the P < 0.05 level. To identify correlations (P < 0.05) between RNA-seq normalized count data and relative qPCR expression, least squares linear regression analyses (SYSTAT12) were also conducted 38 .…”