Demonstration of Innate Immune Responses in the Thyroid Gland: Potential to Sense Danger and a Possible Trigger for Autoimmune Reactions

Abstract

Background: Autoimmune thyroid disease is an archetypal organ-specific autoimmune disorder that is characterized by the production of thyroid autoantibodies and lymphocytic infiltration into the thyroid. However, the underlying mechanisms by which specific thyroid antibodies are produced are largely unknown. Recent studies have shown that innate immune responses affect both the phenotype and the severity of autoimmune reactions. Moreover, it appears that even non-immune cells, including thyroid cells, have an ability to launch such responses. The aim of this study was to conduct a more detailed analysis of innate immune responses of the thyroid upon stimulation with various ''non-self'' and ''self'' factors that might contribute to the initiation of autoimmune reactions. Methods: We used rat thyroid FRTL-5 cells, human thyroid cells, and mice to investigate the effects of various pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and iodide on gene expression and function that were related to innate immune responses. Results: RT-PCR analysis showed that both rat and human thyroid cells expressed mRNAs for Toll-like receptors (TLRs) that sense PAMPs. Stimulation of thyrocytes with TLR ligands resulted in activation of the interferon-beta (IFN-b) promoter and the nuclear factor kappa-light-chain-enhancer of activated B cells (NFjB)-dependent promoter. As a result, pro-inflammatory cytokines, chemokines, and type I interferons were produced. Similar activation was observed when thyroid cells were stimulated with double-stranded DNA, one of the typical DAMPs. In addition to these PAMPs and DAMPs, treatment of thyroid cells with high concentrations of iodide increased mRNA expression of various cytokines. Conclusion: We show that thyroid cells express functional sensors for exogenous and endogenous dangers, and that they are capable of launching innate immune responses without the assistance of immune cells. Such responses may relate to the development of thyroiditis, which in turn may trigger autoimmune reactions.

Apoptosis of NOD.H2h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

“…Highest overexpression (5.77-fold) was observed with the Tpo (thyroid peroxidase) gene. This contrasts with findings from previous studies reporting either no effect of iodide treatment on Tpo expression (23,39,40) or even downregulation of its expression (41,42) in thyroid cells or lines. The reasons for this discrepancy are unclear but may be due to the different protocols used.…”

Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases

“…In addition, poly (I:C) administration aggravates inflammation of excessive iodine-induced thyroiditis in NOD mice, and evidence of the severity of thyroid follicle destruction and amount of lymphocyte infiltration has been reported (25). DNA microarray analysis has shown that stimulation of cultured human thyroid follicles with dsRNA [poly (I:C)] can cause activation of inflammatory responses and upregulation of a variety of related genes, including pro-inflammatory cytokines (IL-6) and chemokines (27). The results of the present study are consistent with previous studies suggesting that TLR3 may be involved in the development of AITD.…”

Ciona intestinalis peroxinectin is a novel component of the peroxidase–cyclooxygenase gene superfamily upregulated by LPS

“…Although a relation between CiPxt and peroxidase activity could be hypothesized, the present data on CiPxt expression by these zones do not allow to establish a relationship between CiPxt gene expression and thyroid-like activity during the inflammatory response. However, it is known that, in humans, proinflammatory cytokines cause thyroid inflammatory disorders (Ajjan et al, 1996) and a recent paper reports on thyroid cells that express functional sensors for exogenous and endogenous dangers, and they are capable of launching innate immune responses without the assistance of immune cells (Kawashima et al, 2012).…”