This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Simons, P. J. Articles by Drexhage, H. A. Search for Related Content PubMed PubMed Citation Articles by Simons, P. J. Articles by Drexhage, H. A.

Antigen-Presenting Dendritic Cells as Regulators of the Growth of Thyrocytes: A Role of Interleukin-1ß and Interleukin-6¹

Department of Immunology, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: P. J. Simons, Lab. Ee 838, Department of Immunology, Faculty of Medicine, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: simons{at}immu.fgg.eur.nl

An accumulation of antigen-presenting dendritic cells (DC) in the thyroid gland, followed by thyroid autoimmune reactivity, occurs in normal Wistar rats during iodine deficiency, and spontaneously in diabetic-prone Biobreeding rats. This intrathyroidal DC accumulation coincides with an enhanced growth rate and metabolism of the thyrocytes, suggesting that both phenomena are related. Because DC are known to regulate the hormone synthesis and growth in other endocrine systems (i.e. the pituitary, the ovary, and the testis), we tested the hypothesis that DC, known for their superb accessory cell function in T cell stimulation, act as regulators of thyrocyte proliferation (and hormone secretion).

We investigated the effect of (Nycodenz density gradient) purified splenic DC from Wistar rats on the growth rate of and thyroid hormone secretion by Wistar thyroid follicles (collagenase dispersion) in culture. Various numbers of DC and follicles were cocultured during 24 h. The proliferative capacity of thyrocytes was measured by adding tritiated thymidine (³H-TdR) and bromodeoxyuridine, the hormone secretion into the culture fluid was measured by using a conventional T₃ RIA. Furthermore, antibodies directed against interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor- (TNF-) were added to these cocultures to determine the role of these cytokines in a possible DC regulation of thyrocyte growth. Cocultures were also carried out in the presence of antimajor histocompatibility complex-class I (MHC I), anti-MHC II, antiintercellular adhesion molecule-1 (ICAM-1), and antilymphocyte function-associated antigen-1 (LFA-1) antibodies to possibly interfere with DC-thyrocyte interactions.

The addition of DC to thyroid follicles clearly inhibited their ³H-TdR uptake, particularly at a 10:1 ratio, in comparison to follicle cultures alone, both under basal conditions and after TSH stimulation (75 ± 7% and 49 ± 11% reduction, respectively, n = 4). The follicle T₃ secretion (after TSH stimulation) was also suppressed by DC in this system, but to a lesser extent (at best at an 1:1 ratio, 25 ± 7% reduction, n = 4). The DC-induced inhibition of thyroid follicle growth was totally abrogated after addition of anti-IL-1ß antibodies; anti-IL-6 only had effect on the DC inhibition of non-TSH-stimulated thyrocytes, whereas anti-TNF- demonstrated no effect at all. The antibodies to MHC and to adhesion molecules had also no effect on this DC-induced growth inhibition. The effect of the different anti-cytokine and anti-adhesion antibodies on the T₃ secretion from thyroid follicles was not investigated.

The clear inhibition of thyrocyte growth by splenic DC (classical antigen-presenting cells) again demonstrates the regulatory role of DC in endocrine systems. Proinflammatory cytokines such as IL-1ß and IL-6 are important mediators in this regulation. The here shown dual role of DC represents a link between the immune and endocrine system, which may form the gateway to the understanding of the initiation of thyroid autoimmune reactions and the thyroid autoimmune phenomena seen in iodine deficiency.

This article has been cited by other articles:

				H. A. Drexhage Are There More than Antibodies to the Thyroid-Stimulating Hormone Receptor that Meet the Eye in Graves' Disease? Endocrinology, January 1, 2006; 147(1): 9 - 12. [Full Text] [PDF]

				J. R. Klein and H.-C. Wang Characterization of a novel set of resident intrathyroidal bone marrow-derived hematopoietic cells: potential for immune-endocrine interactions in thyroid homeostasis J. Exp. Biol., January 1, 2004; 207(1): 55 - 65. [Abstract] [Full Text] [PDF]

				F. G. A. Delemarre, P. G. Hoogeveen, M. de Haan-Meulman, P. J. Simons, and H. A. Drexhage Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes-prone rat J. Leukoc. Biol., March 1, 2001; 69(3): 373 - 380. [Abstract] [Full Text]