Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates?

Abstract

In teleosts, as in mammals, the immune system is tightly regulated by sexual steroid hormones, such as oestrogens. We investigated the effects of 17β-oestradiol on the expression of several genes related to T cell development and resulting T cell subpopulations in sea bass, Dicentrarchus labrax, for a primary lymphoid organ, the thymus, and two secondary lymphoid organs, the head-kidney and the spleen. In parallel, the oxidative burst capacity was assessed in leucocytes of the secondary lymphoid organs. Apoptosis- and proliferation-related genes, indicative of B and T cell clonal selection and lymphoid progenitor activity, were not affected by elevated oestrogen-levels. Sex-related oestrogen-responsiveness in T cell and antigen-presenting cell markers was observed, the expression of which was differentially induced by oestrogen-exposure in the three lymphoid organs. Remarkably, in the spleen, oestrogen increased regulatory T cell-related gene expression was associated with a decrease in oxidative burst capacity. To the best of our knowledge, this study indicates for the first time that physiological levels of oestrogen are likely to promote immune tolerance by modulating thymic function (i.e., T cell development and output) and peripheral T cells in teleosts, similar to previously reported oestrogenic effects in mammals.

Genistein and estradiol have common and specific impacts on the sea bass (Dicentrarchus labrax) skin-scale barrier

“…In contrast, after 5 days exposure E2 and/or Gen stimulated increased expression levels of immune-related gene transcripts, suggesting an enhanced protective effect of the skin-scale barrier. Our results are in line with the E2 immunomodulatory roles previously reported in mammals and fish that have been linked with a reproductive-immune cross-talk [62,63]. Furthermore, the results demonstrated that exposure to (phyto)estrogens in addition to affecting reproductive parameters as previously described [12,14] most likely also modulate innate immune barriers, with possible adverse outcomes for fish health or survival.…”

Thymus development in the zebrafish (Danio rerio) from an ecoimmunology perspective

“…From mammals, we know that sex steroids influence both thymus differentiation and thymus involution (Staples et al, 1999; Zoller & Kersh, 2006). Recent research has shown that the thymus of fish expresses estrogen receptors and that their thymus development and functionality are sensitive to estrogens (Paiola et al, 2017, 2018; Seemann et al, 2015). Thus, the relation between sex steroids and thymus involution is an intriguing avenue to explore.…”

Prepubertal gonad investment modulates thymus function: evidence in a teleost fish

“…Relative expression of forkhead-box n1 ( foxn1), which is a major TEC marker was analysed relative to the expression of two reference genes: elongation factor α 1 (ef1a) and 40S ribosomal protein S30 ( fau) in a single thymic lobe beginning at 155 and 159 dph for natural or fixed photoperiod and temperature setups, respectively as previously described (Paiola et al, 2018). Ef1a and fau were found to be stably expressed upon oestrogen treatment or reproductive cycle in sea bass in natural conditions (Paiola et al, 2018;Pinto et al, 2018). 155 and 159 dph were the ages when thymus growth provided enough thymocytes to use only one lobe for the immunostaining and the other one was available for gene expression.…”

“…We, therefore, aimed at examining whether: (1) changes in thymus plasticity are governed by both energy trade-off and environmental changes such as reproduction and growth and (2) reproductive differentiation, development and the associated rise of plasmatic sex hormones are correlated with thymus atrophy. In European sea bass Dicentrarchus labrax the reproductive development and associated endocrine changes as well as the thymus development and its oestrogenic regulation have been well described (Blázquez et al, 2008;Carrillo et al, 2009;Paiola et al, 2017Paiola et al, , 2018Romano et al, 2011). Despite some similarities in the oestrogenic regulation of thymus function with mammals, the effects of gonadal development and sexual maturation are mostly unknown (O'Neill, 1989;Paiola et al, 2017Paiola et al, , 2018.…”

“…In European sea bass Dicentrarchus labrax the reproductive development and associated endocrine changes as well as the thymus development and its oestrogenic regulation have been well described (Blázquez et al, 2008;Carrillo et al, 2009;Paiola et al, 2017Paiola et al, , 2018Romano et al, 2011). Despite some similarities in the oestrogenic regulation of thymus function with mammals, the effects of gonadal development and sexual maturation are mostly unknown (O'Neill, 1989;Paiola et al, 2017Paiola et al, , 2018. We therefore investigated the kinetic changes of various thymic parameters in juvenile sea bass in relation to endogenous (reproductive axis, growth and energetic resources) and exogenous (photoperiod and temperature) factors that regulate the physiology of ectothermic organisms, including reproduction and immunity.…”