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Thyroid stimulating hormone β-subunit splice variant is expressed in all fractional subsets of bone marrow hematopoietic cells and peripheral blood leukocytes and is modulated during bacterial infection.
General and Comparative Endocrinology ( IF 2.7 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.ygcen.2020.113495
Austin Weber 1 , Hitesh N Pawar 1 , John R Klein 1
Affiliation  

Thyroid stimulating hormone (TSH), a hormone produced in the anterior pituitary, is used to regulate thyroid hormone secretion. It has been known for over three decades that TSH is made by the cells of the immune system; however, the functional role of immune system TSH is unclear. We previously demonstrated that an alternatively-spliced isoform of TSHβ, referred to as the TSHβ splice variant (TSHβv), is the primary form of TSHβ made by hematopoietic cells in mice and humans. Most studies have linked TSHβv expression to myeloid cells of the immune system; however, it has recently been demonstrated that plasma cells in patients with Hashimoto's thyroiditis may be a source of immune system TSHβv. Here, we demonstrate that TSHβv is expressed in bone marrow precursors of lymphoid cells, monocytes, and granulocytes, as well as in mesenteric lymph node (MLN) cells. Plasma cells generated by in vitro culture with bacterial lipopolysaccharide (LPS), and MLN cells from mice infected with L. monocytogenes expressed TSHβv. There was an increase in the intensity of intracellular TSHβv expression in MLN cells following exposure to LPS, and in the proportion of TSHβv+ CD138+ MLN cells following L. monocytogenes infection. The number of TSHβv+ cells increased in MLN cells, particularly among CD138+ cells, following bacterial infection. This was confirmed by an increase in gene expression of BLIMP-1, the transcription factor for CD138, following infection. Levels of circulating thyroxine dropped significantly in mice 24 hrs post-infection. These findings suggest that immune system TSHβv may contribute to the host immune response during bacterial infection.

中文翻译:

促甲状腺激素 β 亚基剪接变体在骨髓造血细胞和外周血白细胞的所有部分亚群中表达,并在细菌感染期间受到调节。

促甲状腺激素 (TSH) 是一种在垂体前叶产生的激素,用于调节甲状腺激素的分泌。三十多年来,人们都知道 TSH 是由免疫系统细胞制造的。然而,免疫系统TSH的功能作用尚不清楚。我们之前证明了 TSHβ 的另一种剪接同种型,称为 TSHβ 剪接变体 (TSHβv),是小鼠和人类造血细胞产生的 TSHβ 的主要形式。大多数研究将 TSHβv 表达与免疫系统的髓样细胞联系起来;然而,最近已经证明桥本甲状腺炎患者的浆细胞可能是免疫系统 TSHβv 的来源。在这里,我们证明 TSHβv 在淋巴细胞、单核细胞和粒细胞的骨髓前体中表达,以及肠系膜淋巴结 (MLN) 细胞。通过体外培养细菌脂多糖 (LPS) 产生的浆细胞和来自感染了单核细胞增生李斯特氏菌的小鼠的 MLN 细胞表达 TSHβv。暴露于 LPS 后,MLN 细胞中的细胞内 TSHβv 表达强度增加,单核细胞增生李斯特氏菌感染后 TSHβv+ CD138+ MLN 细胞的比例增加。细菌感染后,MLN 细胞中 TSHβv+ 细胞的数量增加,尤其是 CD138+ 细胞中。感染后 BLIMP-1(CD138 的转录因子)基因表达的增加证实了这一点。感染后 24 小时,小鼠的循环甲状腺素水平显着下降。这些发现表明免疫系统 TSHβv 可能有助于细菌感染期间的宿主免疫反应。
更新日期:2020-05-01
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