Thyrotropin Alters T Cell Development in the Thymus in Subclinical Hypothyroidism Mouse Model

Abstract

Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid-stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, was used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls. Importantly, the frequencies of CD4 + and CD8 + single-positive (SP) thymocytes increased 38% and 44%, respectively. We demonstrated that TSH protected thymocytes from apoptosis as evidenced by a significant decrease of Annexin V-positive thymocytes in SCH mice. Further analysis showed that extracellular-regulated kinases (ERK) 1/2 in thymus were activated in SCH mice. With analysis of T cell receptor excision circles (TREC), we found that TSH increased recent thymic emigrants (RTE) in spleen tissue in SCH mice. Thus, these results suggest that TSH promoted T cell development and enhanced the thymic recent output in SCH mice, possibly by suppression of apoptosis of thymocytes, indicating that modification of the ERK signalling pathways.

Clinical presentation and prognosis of COVID-19 in older adults with hypothyroidism: data from the GeroCovid observational study

“…Moreover, patients with hypothyroidism tended to present more frequently kidney dysfunctions, supporting the well-known influence that thyroid hormones have on renal growth, glomerular filtration rate, and renal transport systems [14,15]. When considering the pattern of signs/symptoms at COVID-19 onset, we found that the hypothyroidism group was less likely to present anorexia and low oxygen saturation [16], which is a well-known red flag for COVID-19 greater respiratory involvement and poor prognosis. The latter aspect could be ascribed to a milder cytokine response in patients with thyroid disorders, which may less strongly affect pulmonary function [16,17].…”

“…When considering the pattern of signs/symptoms at COVID-19 onset, we found that the hypothyroidism group was less likely to present anorexia and low oxygen saturation [ 16 ], which is a well-known red flag for COVID-19 greater respiratory involvement and poor prognosis. The latter aspect could be ascribed to a milder cytokine response in patients with thyroid disorders, which may less strongly affect pulmonary function [ 16 , 17 ]. Moreover, the lower prevalence of anorexia could be due to the fact that hypothyroidism is often characterized by reduced resting energy expenditure, weight gain, and appetite loss.…”

Alterations in thymocyte populations under conditions of endotoxin tolerance

“…Numerous studies have indicated that the ERK signaling pathway is closely related to thymocyte development, and its activation also plays key roles in the development of diverse diseases. [ 41 , 42 ] For example, thyroid-stimulating hormone promotes T cell development and enhances recent thymic output in mice with subclinical hypothyroidism, possibly by protecting thymocytes from apoptosis, which is related to ERK pathway activation. [ 41 ] The ERK signaling pathway is closely related to the formation of ET.…”

“…[ 41 , 42 ] For example, thyroid-stimulating hormone promotes T cell development and enhances recent thymic output in mice with subclinical hypothyroidism, possibly by protecting thymocytes from apoptosis, which is related to ERK pathway activation. [ 41 ] The ERK signaling pathway is closely related to the formation of ET. Dual-specificity phosphatase 3 (DUSP3) is a regulator of the innate immune response, and sepsis in DUSP3-deficient mice decreases TNF production and impairs ERK1/2 activation, which enhances the tolerance of the mice to LPS-induced multi-bacterial infection.…”

Novel Splicing of Immune System Thyroid Stimulating Hormone β-Subunit—Genetic Regulation and Biological Importance

“…T 3 stimulates thymocyte proliferation, which may be the consequence of TSH-mediated increase in thyroid hormones (15). In that light, recent studies have documented a protective effect of TSH on thymocyte apoptosis (16). These and other directional interactions of HPT hormones on immunity have been detailed in several review articles (17, 18).…”