Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease

Abstract

The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHβ made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHβ splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

Keywords: Hashimoto disease; hematopoiesis; integrated; systemic regulation and adaptation; thyroid hormones.

Figure 1

Genetic organization of (A, B) mouse and (C, D) human native TSHβ, and (E) mouse and (F) human TSHβv.

Figure 2

Putative splicing mechanism used to generate human TSHβv in cells of the immune system. Donor splice sites in intron 1 and acceptor splice sites in intron 2 remove exon 2. A portion of intron 2 is used for the signal peptide as shown in Figure 1 .

Figure 3

Splenic leukocytes from L. monocytogenes-infected mice but not normal mice traffic to the thyroid. Immunofluorescence analysis of (A) the thyroid and (B) a thyroid perivascular lymph node from a non-infected mouse 24 hours post-cell transfer of CFSE-labeled splenic leukocytes from a L. monocytogenes-infected mouse. (C, D) Thyroid of a non-infected mouse 48 hours post-transfer of spleen cells from a L. monocytogenes-infected mouse. CFSE-labeled leukocytes are present surrounding thyroid follicles. (E, F) Thyroid of a non-infected mouse injected with CFSE-labeled spleen cells from a non-infected mouse. TF, thyroid follicle; LN, lymph node.