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Eur J Immunol. 2015 Dec;45(12):3237-40. doi: 10.1002/eji.201546098.

Switching on the Aire conditioner.

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Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology, Tokyo, Japan.


Aire has been cloned as the gene responsible for a hereditary type of organ-specific autoimmune disease. Aire controls the expression of a wide array of tissue-restricted Ags by medullary thymic epithelial cells (mTECs), thereby leading to clonal deletion and Treg-cell production, and ultimately to the establishment of self-tolerance. However, relatively little is known about the mechanism responsible for the control of Aire expression itself. In this issue of the European Journal of Immunology, Haljasorg et al. [Eur. J. Immunol. 2015. 45: 3246-3256] have reported the presence of an enhancer element for Aire that binds with NF-κB components downstream of the TNF receptor family member, RANK (receptor activator of NF-κB). The results suggest that RANK has a dual mode of action in Aire expression: one involving the promotion of mTEC differentiation and the other involving activation of the molecular switch for Aire within mature mTECs.


Aire; Enhancer; NF-κB; Receptor activator of NF-κB; Thymic medulla

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