TY - JOUR AU - Le Texier, Laƫtitia AU - Lineburg, Katie E. AU - Cao, Benjamin AU - McDonald-Hyman, Cameron AU - Leveque-El Mouttie, Lucie AU - Nicholls, Jemma AU - Melino, Michelle AU - Nalkurthi, Blessy C. AU - Alexander, Kylie A. AU - Teal, Bianca AU - Blake, Stephen J. AU - Souza-Fonseca-Guimaraes, Fernando AU - Engwerda, Christian R. AU - Kuns, Rachel D. AU - Lane, Steven W. AU - Teng, Michele AU - Teh, Charis AU - Gray, Daniel AU - Clouston, Andrew D. AU - Nilsson, Susan K. AU - Blazar, Bruce R. AU - Hill, Geoffrey R. AU - MacDonald, Kelli P.A. T1 - Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease PY - 2016/09/22/ AB - Regulatory T cells (Tregs) play a crucial role in the maintenance of peripheral tolerance. Quantitative and/or qualitative defects in Tregs result in diseases such as autoimmunity, allergy, malignancy, and graft-versus-host disease (GVHD), a serious complication of allogeneic stem cell transplantation (SCT). We recently reported increased expression of autophagy-related genes (Atg) in association with enhanced survival of Tregs after SCT. Autophagy is a self-degradative process for cytosolic components that promotes cell homeostasis and survival. Here, we demonstrate that the disruption of autophagy within FoxP3+ Tregs (B6.Atg7fl/fl-FoxP3cre+) resulted in a profound loss of Tregs, particularly within the bone marrow (BM). This resulted in dysregulated effector T cell activation and expansion, and the development of enterocolitis and scleroderma in aged mice. We show that the BM compartment is highly enriched in TIGIT+ Tregs and that this subset is differentially depleted in the absence of autophagy. Moreover, following allogeneic SCT, recipients of grafts from B6.Atg7fl/fl-FoxP3cre+ donors exhibited reduced Treg reconstitution, exacerbated GVHD, and reduced survival compared with recipients of B6.WT-FoxP3cre+ grafts. Collectively, these data indicate that autophagy-dependent Tregs are critical for the maintenance of tolerance after SCT and that the promotion of autophagy represents an attractive immune-restorative therapeutic strategy after allogeneic SCT. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.86850 VL - 1 IS - 15 UR - https://doi.org/10.1172/jci.insight.86850 PB - The American Society for Clinical Investigation ER -