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

Abstract

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.