Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease
| العنوان: | Autophagy-dependent regulatory T cells are critical for the control of graft-versus-host disease |
|---|---|
| المؤلفون: | Rachel D. Kuns, Benjamin Cao, Kylie A. Alexander, Charis E Teh, Katie E. Lineburg, Jemma Nicholls, Laetitia Le Texier, Michele Teng, Bianca E. Teal, Bruce R. Blazar, Kelli P. A. MacDonald, Geoffrey R. Hill, Steven W. Lane, Stephen J. Blake, Michelle Melino, Susan K. Nilsson, Andrew D. Clouston, Lucie Leveque-El Mouttie, Fernando Souza-Fonseca-Guimaraes, Christian R. Engwerda, Cameron McDonald-Hyman, Daniel H.D. Gray, Blessy C. Nalkurthi |
| المصدر: | JCI insight. 1(15) |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, T cell, medicine.medical_treatment, Graft vs Host Disease, chemical and pharmacologic phenomena, Hematopoietic stem cell transplantation, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, Immune tolerance, 03 medical and health sciences, Mice, TIGIT, Bone Marrow, medicine, Autophagy, Immune Tolerance, Animals, Mice, Inbred BALB C, Hematopoietic Stem Cell Transplantation, Peripheral tolerance, FOXP3, General Medicine, medicine.disease, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Graft-versus-host disease, surgical procedures, operative, Immunology, Female, Research Article |
| الوصف: | 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. |
| تدمد: | 2379-3708 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54f95e0e0f7c61124d41f9daceb31a35 https://pubmed.ncbi.nlm.nih.gov/27699243 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....54f95e0e0f7c61124d41f9daceb31a35 |
| قاعدة البيانات: | OpenAIRE |
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