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• W3212642565 abstract "Medullary thymic epithelial cells (mTECs) are key antigen-presenting cells mediating T cell tolerance to prevent harmful autoimmunity. mTECs both negatively select self-reactive T cells and promote the development of thymic regulatory T cells (tTregs) that mediate peripheral tolerance. The relative importance of these two mechanisms of thymic education to prevent autoimmunity is unclear. We generated a mouse model to specifically target the development and function of mTECs by conditional ablation of the NF-κB–inducing kinase (NIK) in the TEC compartment. In contrast to germline-deficient NIK−/− mice, Foxn1CreNIKfl/fl mice rapidly developed fatal T cell–dependent multiorgan autoimmunity shortly after birth. Thymic transplantation and adoptive transfer experiments demonstrated that autoimmunity arises specifically from the emergence of dysfunctional tTregs. Thus, Treg function, rather than negative selection, enforces the protection of peripheral tissues from autoimmune attack." @default.
• W3212642565 created "2021-11-22" @default.
• W3212642565 creator A5025746046 @default.
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• W3212642565 date "2021-11-26" @default.
• W3212642565 modified "2023-10-10" @default.
• W3212642565 title "Protection against autoimmunity is driven by thymic epithelial cell–mediated regulation of T_regdevelopment" @default.
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• W3212642565 doi "https://doi.org/10.1126/sciimmunol.abf3111" @default.

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