Interactions between the immune system and the thyroid. Regulatory networks in health and disease.

Abstract

Hashimoto's thyroiditis, primary myxedema and Graves' disease are thyroid disease that are due to autoimmune reactions towards thyroidal antigens such as thyroid peroxidase (TPO), thyroglobulin (Tg) and the TSH receptor. Thyrocyte destruction in Hashimoto's thyroiditis and primary myxedema is caused by TPO- and Tg-specific lymphocytes and autoantibodies, thyrocyte stimulation in Graves' disease is caused by antibodies stimulating the TSH receptor, thyroid atrophy in primary myxedema is caused by antibodies blocking the TSH receptor, or a yet unknown thyroid growth receptor. The above listed thyroid autoimmune diseases are familial (genetically determined), and due to defects in the immunoregulatory mechanisms that should normally control excessive thyroid autoimmune reactivity. This control towards thyroidal antigens (tolerance) can be broken by professional antigen presenting cells, such as the dendritic cells. It is now known that thyroid autoimmune diseases are indeed initiated by dendritic cells: dendritic cells are present in low number in normal thyroids, but accumulate very early in thyroids that are later affected by thyroid autoimmune disease. Dendritic cells are also present in the normal anterior pituitary and in this gland they are known as the (folliculo) stellate cells, the regulators of growth and function of the surrounding pituitary-endocrine cells. It is discussed whether the influx and clustering of dendritic cells in the thyroid observed during early autoimmune thyroid disease is meant for the regulation of growth and function of the thyrocytes thus linking a putative early endocrine disturbance to the initiation of thyroid autoimmune disease.