Integrative study of hypothalamus–pituitary–thyroid–immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway

Abstract

Thyroid hormones play critical roles in differentiation, growth and metabolism, but their participation in immune system regulation has not been completely elucidated. Modulation of in vivo thyroid status was used to carry out an integrative analysis of the role of the hypothalamus-pituitary-thyroid (HPT) axis in T and B lymphocyte activity. The participation of the protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyperthyroid mice displayed higher Tand B-cell mitogen-induced proliferation, and those from hypothyroid mice displayed lower T-and B-cell mitogeninduced proliferation, compared with euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered the proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher in T and B cells from hyperthyroid mice, and lower in cells from hypothyroid mice, compared with controls. Levels of thyroid-stimulating (TSH) and TSHreleasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBCs) and re-stimulation, in vitro spleen cells from hyper-or hypothyroid mice showed, respectively, increased or decreased production of interleukin (IL)-2 and interferon (IFN)-cytokines. Additionally, an increase in IL-6 and IFN-levels was found in hyperthyroid cells after in vivo injection and in vitro re-stimulation with lipopolysaccharide (LPS).Our results show for the first time a thyroid hormonemediated regulation of PKC content and of cytokine production in lymphocytes; this regulation could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. The results also confirm the important role that these hormones play in regulating lymphocyte reactivity.

Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55–70 years

“…T 3 was also associated with lower incidence of early lymphocyte apoptosis indicating that this thyroid hormone may also facilitate maintenance of the lymphocyte population. Although evidence for thyroid hormone regulation of lymphocyte responses has been demonstrated previously in animal models (Klecha et al 2000(Klecha et al , 2006, the underlying cellular mechanisms are not clearly understood.…”

Adaptive response to Eimeria acervulina in rearing hens is affected by suboptimal incubation temperature and heat exposure in later life

“…Heat-exposed chickens also had lower plasma T 3 levels and higher T 4 levels just before infection compared with control chickens. In addition to the role of thyroid hormones in metabolism, they are also known to be involved in the functioning of the immune system, especially in regulating lymphocyte reactivity (Klecha et al, 2006). Immune responses to E. acervulina are mostly cell dependent (Dalloul and Lillehoj, 2005) and therefore immune modulation by changes in thyroid hormones might be a reason for the significant difference in BW gain in response to Eimeria between heat-exposed and control chickens.…”

Dysfunction of Maternal Thyroid Hormones and Psychiatric Symptoms

“…These changes can be attributed to the effect of thyroid disorders (hyperthyroidism or hypothyroidism) on the immune system. Hypothyroidism can cause several abnormalities as the following (Klecha et al, 2000(Klecha et al, & 2006De Vito et al, 2011): (1) increase the levels of reactive oxygen species (ROS); (2) augmentation of phagocytosis; (3) elevate the activities of the proinflammatory markers such as interleukin-1β and macrophage inflammatory protein-1α; (4) decrease the activities of the antioxidant enzymes; (5) reduce the lymphocyte proliferation parameters; (6) diminish the cell migration and the production of antibody; and (7) decrease the immune response. As well, hyperthyroidism can reduce the activities of the proinflammatory markers such as monocytes and macrophages (Klecha et al, 2008;De Vito et al, 2012).…”