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- Alegre 2019 Am J Transplant + (Literature Watch 969 BY MARIA-LUISA ALEGRE … Literature Watch 969</br>BY MARIA-LUISA ALEGRE, MD, PHD</br>Regulatory T cells that express the transcription factor FoxP3 (Tregs) are essential for the maintenance of immune homeostasis. A lack of Tregs at birth, Treg deletion in adulthood or the selective ablation of the T cell receptor (TCR) in Tregs or of key membrane-associated or signaling molecules, such as CTLA-4, CD28 or PTEN, have been shown in mice to lead to dramatic lymphoproliferative disease, tissue infiltration by activated conventional T cells (Tconvs) and, in many cases, animal death. This underscores the importance of continuous and proper activation of Tregs throughout life. Tregs have a unique metabolic profile, including greater mitochondrial metabolism than Tconvs. Weinberg and colleagues investigate whether mitochondrial respiration (Figure 1) is necessary for the ability of Tregs to maintain homeostasis, and find that tampering with Treg–mitochondrial complex III triggers fatal autoimmunity.l complex III triggers fatal autoimmunity.)