Question

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare disease in which there is autoimmune destruction of several endocrine organs. This disease is caused by mutations in the autoimmune regulator gene called AIRE. AIRE is normally expressed primarily in the thymus and serves as a transcription factor in thymic epithelial cells. A failure to produce AIRE leads to a failure in tolerance to several self-proteins. Which ONE of the following statements best explains the influence of AIRE on self-tolerance?

	a.	AIRE up-regulates expression of proteins usually expressed only in peripheral organs, allowing presentation of the proteins to developing T cells.
	b.	AIRE up-regulates expression of cytokines that inhibit activation of T cells.
	c.	AIRE up-regulates expression of proteins that induce proliferation of thymic epithelial cells, allowing greater self-antigen presentation to T cells.
	d.	AIRE up-regulates expression of MHC proteins, allowing for greater self-antigen presentation to developing T cells.
	e.	AIRE up-regulates expression of Fas ligand on thymic epithelial cells to induce apoptosis in self-reactive T cells.

Answer 1

The statements best explains the influence of AIRE on self-tolerance is

a)AIRE up-regulates expression of proteins usually expressed only in peripheral organs, allowing presentation of the proteins to developing T cells.

In peripheral sites, AIRE was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus. The classical function of these proteins prevents autoimmunity in healthy organisms at two distinct stages during the development and function of T cells. The expression of non-local proteins by AIRE in the thymus reduces the threat of autoimmunity by promoting the elimination of auto-reactive T cells that bind antigens not normally found in the thymus. Peripheral tolerance ensures that self-reactive T cells that escape central tolerance checkpoints remain innocuous in peripheral organs.