Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).

We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire.
PMID: 28931462 [PubMed - as supplied by publisher]

Source: Journal of Autoimmunity - September 17, 2017 Category: Allergy & Immunology Authors: Nishijima H, Kajimoto T, Matsuoka Y, Mouri Y, Morimoto J, Matsumoto M, Kawano H, Nishioka Y, Uehara H, Izumi K, Tsuneyama K, Okazaki IM, Okazaki T, Hosomichi K, Shiraki A, Shibutani M, Mitsumori K, Matsumoto M Tags: J Autoimmun Source Type: research